Methods of modulating mesenchymal stem cell differentiation

ABSTRACT

The present disclosure includes compositions and methods for modulating the differentiation of cells having osteogenic differentiation potential (such as mesenchymal stem cells (MSCs)) towards the osteogenic fate, and for obtaining diagnostic and prognostic information relating to diseases and disorders characterized by defects in osteogenic differentiation. The compositions include miRNAs, rm′RNA mimics, miRNA inhibitors, and siRNAs.

RELATED APPLICATION INFORMATION

This application is a National Stage Application of PCT/US2008/072491, filed Aug. 7, 2008, and claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 60/954,963, filed Aug. 9, 2007, and also claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/034,926, filed Mar. 7, 2008, and also claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/035,253, filed Mar. 10, 2008, each of which is entitled “Methods of modulating mesenchymal stem cell differentiation.” The disclosures of each prior application are incorporated herein by reference in their entirety. To the extent appropriate, a claim of priority is made to each of the above disclosed applications.

FIELD OF THE DISCLOSURE

The present disclosure relates to the field of mesenchymal stem cell (MSC) differentiation. In particular, the disclosure provides a method of directing MSCs (and other cell type having osteogenic potential) toward osteogenic differentiation, or inhibiting MSCs (and other cell type having osteogenic potential) from osteogenic differentiation, using microRNA (miRNA) inhibitors, mimics, and siRNA.

BACKGROUND

Mesenchymal stem cells (MSCs) are capable of differentiating into a wide range of cell types including those associated with the bone development and maintenance (osteoblasts, osteocytes), cartilage, tendons, muscle, adipose, and more. The pluripotent nature of MSCs makes them a potentially valuable tool in therapeutics, particularly in the fields of disease (e.g. osteogenesis imperfecta), tissue repair and regeneration.

The molecular mechanisms underlying MSC differentiation are poorly understood. Microarray profiling studies have clearly identified genomic profiles that distinguish mother and daughter cell lineages, yet the triggers that orchestrate these processes have not been identified.

RNA interference (RNAi) is a near-ubiquitous pathway involved in post-transcriptional gene modulation. A key effector molecule of RNAi is the microRNA (miRNA or miR). These small, non-coding RNAs are transcribed as primary miRNAs (pri-miRNA) and processed in the nucleus by Drosha (a Type III ribonuclease) to generate short hairpin structures referred to as pre-miRNAs. The resulting molecules are transported to the cytoplasm and processed by a second nuclease (Dicer) before being incorporated into the RNA Induced Silencing Complex (RISC). Interaction between the mature miRNA-RISC complex and messenger RNA (mRNA), particularly between the seed region of the miRNA guide strand (nucleotides 2-7) and regions of the 3′ UTR of the mRNA, leads to gene knockdown by transcript cleavage and/or translation attenuation.

SUMMARY

In one aspect, the disclosure provides a method of promoting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate. The method comprises introducing into a MSC an effective amount of a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7.

In another aspect, the disclosure provides a method of inhibiting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate. The method comprises introducing into a MSC an effective amount of a composition comprising at least one differentiation inhibitor selected from the group consisting of mimics of miR-489, mimics of miR-27a, siRNA specific for genes from Tables 2-5, and inhibitors of miR-148b.

In another aspect, the disclosure provides a pharmaceutical composition comprising at least one MSC differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitor of miR-27a, siRNAs specific for genes from Tables 6-7, mimics of miR-148b, and further comprising at least one pharmaceutically acceptable excipient.

In another aspect, the disclosure provides a pharmaceutical composition comprising at least one MSC differentiation inhibitor selected from the group consisting of mimics of miR-489, mimics of miR-27a, siRNAs specific for genes from Tables 2-5, and inhibitors of miR-148b, and further comprising at least one pharmaceutically acceptable excipient.

In another aspect, the disclosure discloses the use of at least one of an inhibitor of miR-489, an inhibitor of miR-27a, a mimic of miR-148b, or a siRNA specific for a gene from Tables 6-7 in the manufacture of a medicament for promoting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate.

In another aspect, the disclosure discloses the use of at least one of a mimic of miR-489, a mimic of miR-27a, a siRNA specific for a gene from Tables 2-5, or an inhibitor of miR-148b in the manufacture of a medicament for inhibiting mesenchymal stem cell (MSC) differentiation toward the osteogenic cell fate.

In another aspect, the disclosure provides a method for treating an individual suffering from a disease characterized by a decreased degree of mesenchymal stem cell (MSC) differentiation relative to a normal individual. The method comprises administering to an individual in need thereof a pharmaceutically effective amount of a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7.

In another aspect, the disclosure provides a method for treating an individual suffering from a disease characterized by an increased degree of mesenchymal stem cell (MSC) differentiation relative to a normal individual. The method comprises administering to an individual in need thereof a pharmaceutically effective amount of a composition comprising at least one differentiation inhibitor selected from the group consisting of a mimic of miR-489, a mimic of miR-27a, a siRNA specific for a gene from Tables 2-5, and an inhibitor of miR-148b.

In another aspect, the disclosure provides a method for obtaining diagnostic or prognostic information relating to a disease characterized by an abnormal degree of mesenchymal stem cell (MSC) differentiation. The method comprises 1) determining the expression level of at least one miRNA selected from the group consisting of miR-148b, miR-489, and miR-27a in an individual suspected of having the disease; and 2) comparing the expression level of the at least one miRNA with that observed in a normal individual known to not have the disease, whereby diagnostic or prognostic information may be obtained.

In another aspect, the disclosure provides a method for obtaining diagnostic or prognostic information relating to a disease characterized by an abnormal degree of mesenchymal stem cell (MSC) differentiation. The method comprises 1) determining the expression level of at least one gene from Tables 2-7 in an individual suspected of having the disease; and 2) comparing the expression level of the at least gene with that observed in a normal individual known to not have the disease, whereby diagnostic or prognostic information may be obtained.

In another aspect, the disclosure provides an isolated mesenchymal stem cell (MSC) comprising at least one differentiation modulating agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, siRNAs specific for genes from Tables 6-7, mimics of miR-489, mimics of miR-27a, siRNA specific for genes from Tables 2-5, and inhibitors of miR-148b.

In another aspect, the disclosure provides a method for performing a bone graft at a site in an individual in need thereof. The method comprises 1) introducing into a mesenchymal stem cell (MSC) ex vivo an effective amount of a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7; and 2) transplanting the MSC into the individual at the site.

In another aspect, the disclosure provides a method of promoting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate. The method comprises at least partially inhibiting in a MSC the expression of a gene selected from the group consisting of ARSE, COL2A1, FBN1, GHRHR, HOXA2, HOXA5, LECT1, NOG, OSTF1, PAPSS2, TFIP11, and TRPS1 using RNA interference.

In another aspect, the disclosure provides a method of inhibiting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate. The method comprises at least partially inhibiting in a MSC the expression of a gene selected from the group consisting of ADAMTS4, AHSG, ALPL, BMI1, CHRD, DLX5, HOXA13, MATN1, MINPP1, PEX7, PRKRA, THRA, AMELY, BMP7, CDH11, CHRD, CHRDL2, EN1, MAPK8, MGP, PAX1, POSTN, SPP1, SUFU, TRAPPC2, TWIST1, GCA, and SLC22A2 using RNA interference.

In another aspect, the disclosure provides a method for increasing osteogenesis in individual. The method comprises administering to an individual in need thereof a pharmaceutically effective amount of at least one mesenchymal stem cell (MSC) differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7.

In another aspect, the disclosure provides a method of promoting differentiation towards the osteogenic cell fate of a cell having osteogenic potential. The method comprising introducing into the cell an effective amount of a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7.

In another aspect, the disclosure provides a method of inhibiting differentiation towards the osteogenic cell fate of a cell having osteogenic potential. The method comprises introducing into the cell an effective amount of a composition comprising at least one differentiation inhibitor selected from the group consisting of mimics of miR-489, mimics of miR-27a, siRNA specific for genes from Tables 2-5, and inhibitors of miR-148b.

In another aspect, the disclosure provides mimics and inhibitors of miR-148b, mimics and inhibitors of miR-489, mimics and inhibitors of miR-27a (including, but not limited to, the mimics and inhibitors of Table 1), and siRNAs specific for the genes of Tables 2-7.

Other aspects to the disclosure are provided below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Inhibitor Screen.

Approximately 400 human miRNA inhibitors targeting human miRNAs (derived from miRbase, at the http site //microrna/sanger.ac.uk.sequences) were transfected into human MSC cells in differentiation media to assess the importance of various miRNAs to MSC osteogenic differentiation. Cultures that exhibited two-fold greater or lesser levels of alkaline phosphatase expression in this primary screen were identified as playing a role in MSC differentiation. X-axis represents individual miRNA inhibitors tested. Y-axis represents the z-score for each inhibitor relative to controls. Studies were performed in triplicate.

FIGS. 2A-2G. Identification of miRNA Inhibitor and Mimic Pairs that Alter MSC Osteogenic Differentiation.

FIG. 2A provides a graph showing inhibitor (I) and mimic (M) pairs that induce opposite effects in the MSC osteogenic differentiation assay. Studies were performed in differentiation media. For hsa-miR-489 and hsa-miR-27a, inhibitors increase alkaline phosphatase (AP) expression and mimics decrease AP expression (Note: 100% represents the amount of activity observed in control experiments). In contrast, an inhibitor of hsa-miR148b decreases alkaline phosphatase expression while a mimic greatly enhances AP expression. FIG. 2B provides a graph showing that the effects of miRNA-27a inhibitors at different doses. FIG. 2C provides a graph showing the effects of miRNA-148b inhibitors at different doses. FIG. 2D provides a graph showing the effects of miRNA-489 inhibitors at different doses. FIG. 2E provides a graph showing the effects of miRNA-27a mimics at different doses. FIG. 2F provides a graph showing the effects of miRNA-148b mimics at different doses. FIG. 2G provides a graph showing the effects of miRNA-489 mimics at different doses. Inhibitors for miR148b and miR 489 exhibit a strong dose dependency. Mimics for miR-27a, miR-148b, and miR-489 all exhibit dose dependency. All experiments were performed in triplicate.

FIGS. 3A-3B. Induction of Osteocyte Differentiation from MSC can Take Place in Both Differentiation Media and Propagation Media.

FIGS. 3A-3B depict graphs that show the percentage of alkaline phosphatase positive cells (Y axes) obtained using various combinations of inhibitors and mimics in the presence of differentiation media and propagation media (“UN-Diff”). The boxed regions shows the ability of miR489 and miR27a inhibitors (“i489” and “i27” respectively), as well as miR148b mimics (“m148b”) to induce osteogenic differentiation in propagation media (FIG. 3A) and differentiation media (FIG. 3B). See control inhibitors (“ic1”) and control mimics (“mc1”) for comparison. FIGS. 3A and 3B demonstrate the ability of these molecules to induce differentiation under both conditions. FIG. 3A also demonstrates the ability of various combinations of molecules to act additively to provide enhanced levels of osteogenic differentiation. Pairs of molecules including 1) i489+i27a, 2) i489+m148b, and 3) i27a+m148b (25 nM of each, 50 nM total), or a combination of all three molecules (i489+i27a+m148b, 25 nM each, 75 nM total) were compared with the effects of individual inhibitors or mimics (i489, i27a, or m148b, 25 nM). The results show that one combination of molecules (i489+m148b) induces greater number of cells to undergo osteogenic differentiation than either of the individual molecule treatments (i.e. i489 or m148b). In FIGS. 3A-3B, the letters “i”, “m”, and “c” symbolize “inhibitor”, “mimic”, and “control”, respectively.

FIG. 4. siRNA-Mediated Knockdown of Genes Targeted By miR-27a, miR-489, and miR-148b.

FIG. 4 provides a graphical representation of the effects of siRNA mediated knockdown of genes targeted by miRNAs of the disclosure. siRNAs targeting CHRD, GCA and SLC22A2 (targets of miRNAs 27a and 489) leads to a decrease in MSC differentiation as measured by AP expression. In contrast, siRNA mediated knockdown of NOG leads to an increase in MSC differentiation as measured by AP expression. UNTR indicates untreated cells.

FIGS. 5A-5B. Summary of the Activity of miRs, miR Mimics, siRNAs, miRNA Inhibitors, and Genes in Modulating MSC Differentiation.

FIG. 5A depicts schematically the roles of the miRs identified by the disclosure (miR-148b, miR-489, miR-27a) in MSC differentiation. Specifically, MSC differentiation towards the osteogenic cell fate is promoted by miR-148b and is inhibited by miR-489 and miR-27a. FIG. 5B depicts schematically the MSC differentiation promoting or inhibiting activity of various agents identified in the disclosure. Specifically, MSC differentiation is promoted by miR-148b mimics, miR-489 inhibitors, miR-27a inhibitors, and by siRNAs and miRNAs (and other mediators of RNAi) specific for the genes of Tables 6-7. MSC differentiation is inhibited by miR-489 mimics, miR-27a mimics, miR-148b inhibitors, and by siRNAs and miRNAs (and other mediators of RNAi) specific for the genes of Tables 2-5.

DETAILED DESCRIPTION

All references referred to herein are specifically incorporated herein in their entirety.

DEFINITIONS

The terms “alkaline phosphatase,” “ALP,” or “AP” are interchangeable and refer to a hydrolase enzyme responsible for removing phosphate groups from many types of molecules. As the name suggests, alkaline phosphatases are most effective in an alkaline environment.

The term “differentiate” refers to the process cells undergo to become a more specialized cell type.

The term “gene silencing” refers to a process by which the expression of a specific gene product is lessened or attenuated by RNA interference. The level of gene silencing (also sometimes referred to as the degree of “knockdown”) can be measured by a variety of means, including, but not limited to, measurement of transcript levels by Northern Blot Analysis, B-DNA techniques, transcription-sensitive reporter constructs, expression profiling (e.g. DNA chips), qRT-PCR and related technologies. Alternatively, the level of silencing can be measured by assessing the level of the protein encoded by a specific gene. This can be accomplished by performing a number of studies including Western Analysis, measuring the levels of expression of a reporter protein that has e.g. fluorescent properties (e.g., GFP) or enzymatic activity (e.g. alkaline phosphatases), or several other procedures.

The term “mesenchymal stem cell” or “MSC” refers to pluripotent stem cells that can be derived from a variety of species (e.g. human, mouse, rat) and that can differentiate into osteoblasts, chondrocytes, myocytes, adipocytes and more. Typical MSC molecular markers can vary considerably depending upon the tissue origin of the cells, but can include CD29 and CD105. MSCs can be derived from a number of tissues including, but not limited to, bone marrow, cartilage, tendon, muscle, and adipose tissues.

The term “microRNA”, “miRNA”, and “miR” are synonymous and refer to a collection of non-coding single-stranded RNA molecules of about 19-28 nucleotides in length, which regulate gene expression. miRNAs are found in a wide range of organisms (from viruses to humans) and have been shown to play a role in development, homeostasis, and disease etiology. MicroRNAs are processed from single stranded primary transcripts known as pri-miRNA to short stem-loop structures (hairpins) called pre-miRNA and finally to mature miRNA. One or both strands of the mature miRNA molecules are partially complementary to one or more messenger RNA (mRNA) molecules, and function to downregulate gene expression by either cleavage or translation attenuation mechanisms.

The term “mature strand” refers to the strand of a fully processed miRNA, or an siRNA that enters RISC. In some cases, miRNAs have a single mature strand that can vary in length between about 17-28 nucleotides in length. In other instances, miRNAs can have two mature strands (i.e. two unique strands that can enter RISC), and the length of the strands can vary between about 17 and 28 nucleotides. In the present disclosure, the terms “mature strand,” “guide strand” and “antisense strand” are used interchangeably.

The term “miRNA seed” or “seed” refers to a region of the mature strand(s) of a microRNA or microRNA mimic. The region generally includes nucleotides 2-6 or 2-7 counting from the 5′ end of the mature strand.

The term “miRNA seed complement” or “seed complement” refers to a sequence of nucleotides in a target gene, preferably in the 3′ UTR of a target gene, that is complementary to some or all of the miRNA seed.

The term “nucleotide” refers to a ribonucleotide or a deoxyribonucleotide or modified form thereof, as well as an analog thereof. Nucleotides include species that comprise purines, e.g., adenine, hypoxanthine, guanine, and their derivatives and analogs, as well as pyrimidines, e.g., cytosine, uracil, thymine, and their derivatives and analogs. Nucleotide analogs include nucleotides having modifications in the chemical structure of the base, sugar and/or phosphate, including, but not limited to, 5-position pyrimidine modifications, 8-position purine modifications, modifications at cytosine exocyclic amines, and substitution of 5-bromo-uracil; and 2′-position sugar modifications, including but not limited to, sugar-modified ribonucleotides in which the 2′-OH is replaced by a group such as an H, OR, R, halo, SH, SR, NH₂, NHR, NR₂, or CN, wherein R is an alkyl moiety. Nucleotide analogs are also meant to include nucleotides with bases such as inosine, queuosine, xanthine, sugars such as 2′-methyl ribose, non-natural phosphodiester linkages such as in ethylphosphonates, phosphorothioates and peptides.

Modified bases refer to nucleotide bases such as, for example, adenine, guanine, cytosine, thymine, uracil, xanthine, inosine, and queuosine that have been modified by the replacement or addition of one or more atoms or groups. Some examples of types of modifications that can comprise nucleotides that are modified with respect to the base moieties include but are not limited to, alkylated, halogenated, thiolated, aminated, amidated, or acetylated bases, individually or in combination. More specific examples include, for example, 5-propynyluridine, 5-propynylcytidine, 6-methyladenine, 6-methylguanine, N,N,-dimethyladenine, 2-propyladenine, 2-propylguanine, 2-aminoadenine, 1-methylinosine, 3-methyluridine, 5-methylcytidine, 5-methyluridine and other nucleotides having a modification at the 5 position, 5-(2-amino)propyl uridine, 5-halocytidine, 5-halouridine, 4-acetylcytidine, 1-methyladenosine, 2-methyladenosine, 3-methylcytidine, 6-methyluridine, 2-methylguanosine, 7-methylguanosine, 2,2-dimethylguanosine, 5-methylaminoethyluridine, 5-methyloxyuridine, deazanucleotides such as 7-deaza-adenosine, 6-azouridine, 6-azocytidine, 6-azothymidine, 5-methyl-2-thiouridine, other thio bases such as 2-thiouridine and 4-thiouridine and 2-thiocytidine, dihydrouridine, pseudouridine, queuosine, archaeosine, naphthyl and substituted naphthyl groups, any O- and N-alkylated purines and pyrimidines such as N6-methyladenosine, 5-methylcarbonylmethyluridine, uridine 5-oxyacetic acid, pyridine-4-one, pyridine-2-one, phenyl and modified phenyl groups such as aminophenol or 2,4,6-trimethoxy benzene, modified cytosines that act as G-clamp nucleotides, 8-substituted adenines and guanines, 5-substituted uracils and thymines, azapyrimidines, carboxyhydroxyalkyl nucleotides, carboxyalkylaminoainleotides, and alkylcarbonylalkylated nucleotides. Modified nucleotides also include those nucleotides that are modified with respect to the sugar moiety, as well as nucleotides having sugars or analogs thereof that are not ribosyl. For example, the sugar moieties may be, or be based on, mannoses, arabinoses, glucopyranoses, galactopyranoses, 4′-thioribose, and other sugars, heterocycles, or carbocycles.

The term nucleotide is also meant to include what are known in the art as universal bases. By way of example, universal bases include, but are not limited to, 3-nitropyrrole, 5-nitroindole, or nebularine. The term “nucleotide” is also meant to include the N3′ to P5′ phosphoramidate, resulting from the substitution of a ribosyl 3′-oxygen with an amine group. Further, the term nucleotide also includes those species that have a detectable label, such as for example a radioactive or fluorescent moiety, or mass label attached to the nucleotide.

As used herein, the term “osteogenic differentiation” refers to processes by which cells become progressively more specialized and adopt attributes typically associated with cells of an osteoblast/osteocyte cell lineage. Typically, this process of specialization for the cell comes at the expense of its breadth of differentiation potential and can be monitored by following the expression of a number of molecular markers including, but not limited to, alkaline phosphatase.

The term “osteoblast” and “osteocyte” refers to abundant cell types found in bone.

The term “pluripotent” refers to a cell's ability to differentiate into multiple cell types.

The term “polynucleotide” refers to polymers of two or more nucleotides, and includes, but is not limited to, DNA, RNA, DNA/RNA hybrids including polynucleotide chains of regularly and/or irregularly alternating deoxyribosyl moieties and ribosyl moieties (i.e., wherein alternate nucleotide units have an —OH, then and —H, then an —OH, then an —H, and so on at the 2′ position of a sugar moiety), and modifications of these kinds of polynucleotides, wherein the attachment of various entities or moieties to the nucleotide units at any position are included.

The term “ribonucleotide” and the term “ribonucleic acid” (RNA), refer to a modified or unmodified nucleotide or polynucleotide comprising at least one ribonucleotide unit. A ribonucleotide unit comprises an hydroxyl group attached to the 2′ position of a ribosyl moiety that has a nitrogenous base attached in N-glycosidic linkage at the 1′ position of a ribosyl moiety, and a moiety that either allows for linkage to another nucleotide or precludes linkage.

The term “RNA interference” and the term “RNAi” are synonymous and refer to the process by which a polynucleotide (a miRNA or siRNA) comprising at least one polyribonucleotide unit exerts an effect on a biological process. The process includes, but is not limited to, gene silencing by degrading mRNA, attenuating translation, interactions with tRNA, rRNA, hnRNA, cDNA and genomic DNA, as well as methylation of DNA with ancillary proteins.

The term “siRNA” and the phrase “short interfering RNA” refer to unimolecular nucleic acids and to nucleic acids comprised of two separate strands that are capable of performing RNAi and that have a duplex region that is between 14 and 30 base pairs in length. Additionally, the term siRNA and the phrase “short interfering RNA” include nucleic acids that also contain moieties other than ribonucleotide moieties, including, but not limited to, modified nucleotides, modified internucleotide linkages, non-nucleotides, deoxynucleotides and analogs of the aforementioned nucleotides.

siRNAs can be duplexes, and can also comprise short hairpin RNAs, RNAs with loops as long as, for example, 4 to 23 or more nucleotides, RNAs with stem loop bulges, micro-RNAs, and short temporal RNAs. RNAs having loops or hairpin loops can include structures where the loops are connected to the stem by linkers such as flexible linkers. Flexible linkers can be comprised of a wide variety of chemical structures, as long as they are of sufficient length and materials to enable effective intramolecular hybridization of the stem elements. Typically, the length to be spanned is at least about 10-24 atoms. When the siRNAs are hairpins, the sense strand and antisense strand are part of one longer molecule.

Detailed descriptions of the criteria for the rational design of siRNA antisense strands for efficient gene silencing can be found in WO 2004/045543, WO 2006/006948, WO 2005/078095, WO 2005/097992, and WO 2005/090606, each of which is incorporated herein by reference in its entirety.

siRNAs can target any sequence including protein encoding sequences (e.g., open reading frames, ORFs), and non-coding sequences (e.g., 3′ UTRs, 5′ UTRs, intronic regions, promoter regions, microRNAs, piRNAs, enhancer regions, repetitive sequences, and more). In contrast, microRNA and piRNA mimics of the disclosure generally target a subset of genes and tools for predicting miRNA targets can be found in any number of publications including but not limited to Griffith-Jones, S. et al., Nucleic Acids Research, 2007.

The term “piRNAs” refers to Piwi-interacting RNAs, a class of small RNAs that are believed to be involved in transcriptional silencing (see Lau, N. C. et al (2006) Science, 313:305-306).

The term “z score” refers to a statistical measurement that quantifies the distance (measured in standard deviations) a data point is from the mean of a data set. A z score is a dimensionless quantity derived by subtracting the sample mean from an individual (raw) score and then dividing the difference by the sample standard deviation.

The inventors have identified several microRNAs that participate in determining whether or not MSCs differentiate toward cells of an osteogenic cell fate. In addition, it has been discovered by the inventors that inhibitors and mimics of these microRNAs can be used (singularly or in combination) to induce or inhibit MSC osteogenic differentiation or to prevent MSC differentiation into other cell identities (e.g. adipocytes). In addition, the target genes of those microRNAs have been identified by the inventors (see Tables 2-7), and the inventors have further demonstrated that siRNA-mediated knockdown of those target genes can induce or inhibit MSC osteogenic differentiation in the manner predicted by the microRNA results. Thus, modulation of the expression of those target genes by any method known in the art (e.g., siRNA, piRNA, antisense, antibodies, and aptamers against the proteins produced by the target genes etc), or by using the miRNAs, miRNA mimics, and inhibitors of the disclosure can be used to modulate MSC differentiation, including in a therapeutic or prophylactic context. Moreover, measuring the expression level of the target genes of Tables 2-7 and/or the miRNAs identified herein can yield diagnostic or prognostic medical information relating to diseases or disorders characterized by abnormal degrees of MSC differentiation.

The sequences of currently known human, mouse, and rat miRNAs are available at miRBase which is maintained by the Wellcome Trust Sanger Institute see the http site //microrna.sanger.ac.uk/sequences/. As such, a person of ordinary skill in the art can select a sequence from the database for a desired miRNA and design a mimic useful for the methods disclosed herein.

The miRNAs of the disclosure can be identified as single stranded pri-miRNA or pre-miRNA hairpin structures (wherein a hairpin is defined as an oligonucleotide that is 40-150 nucleotides in length and contains secondary structures that result in regions of duplex and loops) or characterized as mature double stranded miRNAs. The miRNAs are capable of entering the RNAi pathway, being processed by gene products associated with the pathway (e.g., Drosha, Dicer, and the RNA interference Silencing Complex, RISC), and inhibiting gene expression by translation attenuation or message (mRNA) cleavage. As such, all of the miRNAs of the invention can be described by multiple labels depicting the level of processing.

With respect to the sequence of pri-, pre-, and mature miRNA sequences, it is worth noting that the field of RNAi and thus the sequences and structures associated with human, mouse and rat miRNAs varies slightly as versions of the miRNA database evolve. Though these newer versions of e.g. miRbase can have sequences that are extended and/or truncated on either the 5′ or 3′ end of the mature and passenger sequences, the changes do not alter the overall identity of the miRNA nor the ability to utilize these sequences in the context of the described embodiments.

In a first aspect, the present disclosure provides a method of modulating (e.g. inducing/promoting or inhibiting) mesenchymal stem cell osteogenic differentiation by using microRNA inhibitors and/or mimics. The methods of the disclosure may be performed ex vivo or in vivo.

MCS cells can be obtained commercially (e.g. Lonza, Inc) and cultured in vitro using medium (also referred to as a “pro-osteogenic cocktails” or “differentiation media”) that sensitize cells to differentiate. Such media often comprise standard constituents plus dexamethasone, ascorbic acid-2-phosphate, beta-glycerophosphate, or other factors that enhance MSC differentiation. Alternatively, MSCs can be cultured on one or more media that do not sensitize cells toward osteogenic differentiation. Relevant references that pertain to characterization and differentiation of MSCs include: Baksh, D et al. (2004) J. Cell. Mol. Med. 8(3): 301-316; Aggarwal, S. et al. (2005) Blood 105: 1815-22; Akino, K. et al. (2006) Wound Repair Regen. 14:343-9; Jian, H. et al. (2006) Genes Dev. 20:666-74, each of which is incorporated herein by reference in its entirety.

The terms “microRNA inhibitor”, “miR inhibitor”, or “inhibitor” are synonymous and refer to oligonucleotides or modified oligonucleotides that interfere with the ability of specific miRNAs, or siRNAs to silence their intended targets. In general, the inhibitors are nucleic acid or modified nucleic acids in nature including oligonucleotides comprising RNA, modified RNA, DNA, modified DNA, locked nucleic acids (LNAs), or any combination of the above. Modifications include 2′ modifications (including 2′-O alkyl modifications and 2′ F modifications) and internucleotide modifications (e.g. phosphorothioate modifications) that can affect delivery, stability, specificity, intracellular compartmentalization, or potency. In addition, miRNA inhibitors can comprise conjugates that can affect delivery, intracellular compartmentalization, stability, and/or potency.

Inhibitors can adopt a variety of configurations including single stranded, double stranded (RNA/RNA or RNA/DNA duplexes), and hairpin designs. In general, microRNA inhibitors comprise contain one or more sequences or portions of sequences that are complementary or partially complementary with the mature strand (or strands) of the miRNA to be targeted. In addition, the miRNA inhibitor may also comprise additional sequences located 5′ and 3′ to the sequence that is the reverse complement of the mature miRNA. The additional sequences may be the reverse complements of the sequences that are adjacent to the mature miRNA in the pri-miRNA from which the mature miRNA is derived, or the additional sequences may be arbitrary sequences (having a mixture of A, G, C, or U). In some embodiments, one or both of the additional sequences are arbitrary sequences capable of forming hairpins. Thus, in some embodiments, the sequence that is the reverse complement of the miRNA is flanked on the 5′ side and on the 3′ side by hairpin structures. Micro-RNA inhibitors, when double stranded, may include mismatches between nucleotides on opposite strands. Furthermore, micro-RNA inhibitors may be linked to conjugate moieties in order to facilitate uptake of the inhibitor into a cell. For example, a micro-RNA inhibitor may be linked to cholesteryl 5-(bis(4-methoxyphenyl)(phenyl)methoxy)-3 hydroxypentylcarbamate) which allows passive uptake of a micro-RNA inhibitor into a cell. Micro-RNA inhibitors, including hairpin miRNA inhibitors, are described in detail in Vermeulen et al., “Double-Stranded Regions Are Essential Design Components Of Potent Inhibitors of RISC Function,” RNA 13: 723-730 (2007) and in WO2007/095387 and WO 2008/036825 each of which is incorporated herein by reference in its entirety. A person of ordinary skill in the art can select a sequence from the database for a desired miRNA and design an inhibitor useful for the methods disclosed herein. The sequences of known human, mouse, and rat miRNAs discovered by wet-lab experimentation or bioinformatic methods are available at miRBase which is maintained by the Wellcome Trust Sanger Institute (http://microma.sanger.ac.uk/sequences/).

The miRNA inhibitors used in the Examples of this disclosure consisted of single stranded, 54 nucleotides, fully 2′-O-methylated, oligonucleotides having a central region that is complementary to the mature miRNA target sequence and 5′ and 3′ flanking sequences of equivalent length.

Exemplified herein are the inhibitors designed to target hsa-miR-489, hsa-miR-27a, hsa-miR-148b, or any of the closely related family members (see Table 1). As shown in Example 1, transfection of microRNA inhibitors individually targeting the majority of human miRNAs has little or no effect on MSCs osteogenic differentiation. In contrast, transfection of inhibitors targeting hsa-miR-489 or hsa-miR-27a into mesenchymal stem cells enhances the production of alkaline phosphatase, a key cellular marker of osteoblasts. The differentiation is highly specific to osteogenic differentiation and does not include differentiation into other cell types (e.g. adipose cell, hematopoietic cells). Of equal importance, the inventors have discovered that inhibitors of hsa-miR-489, hsa-miR-27a and related family members induce osteogenic differentiation both in the presence and absence of pro-osteogenic cocktails being added to the media (see Example 4). Moreover, inhibitors of hsa-miR-148b (unlike inhibitors of hsa-miR-489 and hsa-miR-27a) are capable of inhibiting osteogenic differentiation.

miRNA mimics represent a class of molecules that can be used to imitate the gene silencing ability of one or more miRNAs. Thus, the term “microRNA mimic” refers to synthetic non-coding RNAs (i.e. the miRNA is not obtained by purification from a source of the endogenous miRNA) that are capable of entering the RNAi pathway and regulating gene expression. miRNA mimics can be designed as mature molecules (e.g. single stranded) or mimic precursors (e.g., pri- or pre-miRNAs). miRNA mimics can be comprised of nucleic acid (modified or modified nucleic acids) including oligonucleotides comprising, without limitation, RNA, modified RNA, DNA, modified DNA, locked nucleic acids, or 2′-O,4′-C-ethylene-bridged nucleic acids (ENA), or any combination of the above (including DNA-RNA hybrids). In addition, miRNA mimics can comprise conjugates that can affect delivery, intracellular compartmentalization, stability, specificity, functionality, strand usage, and/or potency.

In one design, miRNA mimics are double stranded molecules (e.g., with a duplex region of between about 16 and about 31 nucleotides in length) and contain one or more sequences that have identity with the mature strand of a given miRNA. Modifications can comprise 2′ modifications (including 2′-O methyl modifications and 2′ F modifications) on one or both strands of the molecule and internucleotide modifications (e.g. phorphorthioate modifications) that enhance nucleic acid stability and/or specificity. In addition, miRNA mimics can include overhangs. The overhangs can consist of 1-6 nucleotides on either the 3′ or 5′ end of either strand and can be modified to enhance stability or functionality.

In one embodiment, a miRNA mimic comprises a duplex region of between 16 and 31 nucleotides and one or more of the following chemical modification patterns: the sense strand contains 2′-O-methyl modifications of nucleotides 1 and 2 (counting from the 5′ end of the sense oligonucleotide), and all of the Cs and Us; the antisense strand modifications can comprise 2′ F modification of all of the Cs and Us, phosphorylation of the 5′ end of the oligonucleotide, and stabilized internucleotide linkages associated with a 2 nucleotide 3′ overhang.

The mimics used in the Examples of this disclosure are 19-28 bp, double stranded RNA molecules comprising a 5′ phosphorylated antisense strand that is identical to the mature strand of the miRNA under study. In addition, all mimics used in the Examples contain 2′-O-methyl modifications on the first two nucleotides of the 5′ end of the non-targeting strand (also referred to as the passenger strand or the star strand).

In one aspect, the mimic is a mimic of hsa-miR-148b and related family members (see Table 1). As shown in Example 2, transfection of a mimic of hsa-miR-148b into mesenchymal stem cells enhances the production of alkaline phosphatase, a key cellular marker of osteoblasts. Again, the differentiation process is specific to osteogenic differentiation (i.e. cells do not differentiate into other cell lineages). And, as was the case with miRNA inhibitors targeting hsa-miR-489, hsa-miR-27a and related family members, the hsa-miR-148b mimic can induce osteogenic differentiation in the presence and absence of pro-osteogenic cocktails being added to the culture media. Simultaneously, the inventors have discovered that mimics of hsa-miR-489 and hsa-miR27a inhibit MSC osteogenic differentiation.

Thus, in one aspect the disclosure provides a method of promoting MSC differentiation towards the osteogenic cell fate, the method comprising introducing into a MSC (ex vivo or in vivo) a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, and mimics of miR-148b. The miRs, mimics and inhibitors can be used singly or in any combination to promote MSC differentiation. By way of non-limiting example, MSC differentiation may be promoted by introducing (e.g., by transfection, passive uptake etc) into a MSC a composition comprising:

-   -   1. at least one miR-489 inhibitor (e.g. 1, 2, 3, or more         different miR-489 inhibitors);     -   2. at least one miR-27a inhibitor (e.g. 1, 2, 3, or more         different miR-27a inhibitors);     -   3. at least one miR-148b mimic (e.g. 1, 2, 3, or more different         miR-148b mimics);     -   4. at least one miR-489 inhibitor in combination with at least         one miR-27a inhibitor and at least one miR-148b mimic; or     -   5. at least one miR-489 inhibitor in combination with at least         one miR-148b mimic.

In another aspect the disclosure provides a method of inhibiting MSC differentiation toward the osteogenic cell fate, the method comprising introducing into a MSC (ex vivo or in vivo) a composition comprising at least one differentiation inhibitor selected from the group consisting of mimics of miR-489, mimics of miR-27a, and inhibitors of miR-148b. The mimics and inhibitors can be used singly or in any combination to inhibit MSC differentiation. By way of non-limiting example, MSC differentiation may be inhibited by introducing (e.g., by transfection, passive uptake etc) into a MSC a composition comprising:

-   -   1. at least one miR-489 mimic (e.g. 1, 2, 3, or more different         miR-489 mimics);     -   2. at least one miR-27a mimic (e.g. 1, 2, 3, or more different         miR-27a mimics);     -   3. at least one miR-148b inhibitor (e.g. 1, 2, 3, or more         different miR-148b inhibitors);     -   4. at least one miR-489 mimic in combination with at least one         miR-27a mimic and at least one miR-148b inhibitor; or     -   5. at least one miR-489 mimic in combination with at least one         miR-148b inhibitor.

Given the similarities in miRNAs amongst mammalian systems, equivalent mimic and inhibitor molecules derived from different species are expected to have similar effects on their respective organisms.

In another aspect, the disclosure provides inhibitors and mimics of miR-489, miR-27a, and miR-148b including, but not limited to, the mimics and inhibitors of Table 1. In view of the utility of such mimics and inhibitors disclosed herein by the inventors, the design of other mimics and inhibitors of miR-489, miR-27a, and miR-148b is within the skill of the ordinary artisan.

Synthetic mimics and inhibitors can be delivered to cells to influence MSC differentiation by a variety of methods including, but not limited to, lipid (e.g. DharmaFECT1, Thermo Fisher Scientific) or chemical (e.g. calcium phosphate) mediated transfection, electroporation, lipid-independent delivery via conjugation to one or more entities that mediate lipid- or chemical-independent delivery (e.g. conjugation of cholesterol), or any other method that has been identified or will be identified for nucleic acid transfer to target cells. In addition, mimics and inhibitors can be delivered to a cell using a plasmid vector that expresses the sequence(s) that encode the mimic or inhibitor of choice. Such expression vectors can be introduced into cells (including cells within an organism such as a human being) by art-recognized transfection methods (e.g. Lipofectamine 2000, Invitrogen) or via viral-mediated delivery (e.g. lentiviral, adenoviral). One preferred expression system is described in PCT/US2008/64462, which is incorporated herein by reference in its entirety

Studies have demonstrated that not all miRNAs are processed with equal efficiency. For that reason, incorporation of the therapeutic miRNAs (e.g. mimics and inhibitors) of the disclosure into a highly processed scaffold (e.g., miR-196a-2) would ensure efficient processing and expression.

Synthetic mimics and inhibitors may be modified with a wide range of chemical modifications to enhance stability, functionality, cellular uptake, and specificity, and strand usage. For instance, studies presented in U.S. patent application Ser. No. 11/051,195, which is incorporated herein by reference in its entirety, and other documents have identified multiple chemical modification patterns, including 2′-O-methyl modifications, locked nucleic acids (LNAs), morpholinos, ethylene-bridged analogs (ENAs), 2′-F modifications, and phosphorothioate modifications, that greatly enhance the stability of double stranded RNAs in serum. Similarly, addition of 2′-O-methyl modifications to positions 1 and 2 (counting from the 5′ end of the molecule) in the passenger strand can enhance functionality and specificity (see patent application Ser. No. 11/019,831, which is incorporated herein by reference in its entirety).

In some embodiments, the miRNA inhibitor or mimic is conjugated to a lipid molecule such as cholesterol (preferably using a linker) in order to allow passive delivery of the inhibitor to a MSC (in vivo or ex vivo). See WO 2008/036825 which is incorporated herein by reference in its entirety. In preferred embodiments, the mimics and inhibitors contain the modification patterns and conjugate moieties disclosed in WO 2008/036825. For example, in one embodiment, a miRNA mimic of the disclosure comprises an RNA duplex having:

-   -   1. a sense strand that ranges in size from about 18 to about 30         nucleotides wherein nucleotides 1 and 2 (numbered from the 5′         end) are 2′ O-methyl modified and wherein all C nucleotides and         all U nucleotides are 2′O-methyl modified;     -   2. an antisense strand that ranges in size from about 18 to         about 30 nucleotides, wherein all C nucleotides and all U         nucleotides are 2′ F modified, and wherein the antisense strand         has significant levels of complementarity to the sense strand as         well as to the target gene of the endogenous miR;     -   3. a 2 nucleotide overhang at the 3′ end of the antisense strand         comprising phosphorothioate linkages;     -   4. a cholesterol molecule attached to the 3′ end of the sense         strand via a C5 linker molecule wherein the         cholesterol-linker-sense strand can have the structure:

-   -   5. optionally a phosphate group at the 5′ end of the antisense         strand; and     -   6. optionally, a mismatch between at least one of nucleotides 1,         7, and 14 on the antisense strand (numbered from the 5′ end) and         the opposite nucleotide on the sense strand. The cholesterol         molecule allows passive uptake of the mimic into cells.

The mimics and inhibitors of the disclosure can be generated using a range of art-recognized techniques (e.g. ACE chemistry, see U.S. Pat. Nos. 6,111,086; 6,590,093; 5,889,136; and 6,008,400, each of which is incorporated herein by reference in its entirety).

Mimics and inhibitors can be introduced into MSCs either ex vivo (e.g. in vitro) or in vivo (e.g., within a whole organism such as a human being or any other mammal). Thus, in another aspect the disclosure provides isolated cells and isolated tissues comprising the inhibitors and mimics of the disclosure, and also provides isolated, cells and isolated tissues comprising siRNAs specific for the genes disclosed below. Moreover, as detailed below, the mimics and inhibitors of the disclosure can be formulated as pharmaceutical compositions for the treatment (e.g. therapeutic or prophylactic use) of diseases or disorders in which MSC differentiation (or lack thereof) is implicated (e.g. osteogenesis imperfecta) or for the treatment of disease, conditions, and disorders in which increased osteogenesis or decreased osteogenesis is desirable.

The level of osteogenic differentiation by MSCs can be assessed by a variety of methods including 1) measuring alkaline phosphatase activity by one or more enzymatic assays, 2) staining cells with Alizarin-Red S solution or silver nitrate which identifies calcium phosphate deposits, or 3) measuring expression of osteogenic marker genes including osterix, cbfal, osteopontin, osteocalcin, or bone sialoprotein, which can be performed at the RNA or protein level.

Small molecule compounds that have effects on osteogenesis have been shown to exhibit effects in in vivo systems (e.g. TAK-778 [(2R,4S)-(−)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide, see, Notoya, K. et al. (1999) J Pharmacol Exp Ther. 290:1054-64). Thus, the mimics and inhibitors described here will also prove efficacious in whole animal (human and non-human) systems as therapeutic and/or prophylactic agents. Methods for the delivery of miRNA mimics and inhibitors to an organism are known in the art.

In another aspect, the level of expression of one or more of miR-489, miR-27a, and miR-148b (and/or the level(s) of any corresponding pri-miRNA and/or pre-miRNA) is measured. The results of measurements can be used for disease detection, disease diagnosis, disease prognosis (e.g. an estimate of disease outcome), and to determine or predict the efficacy of a therapeutic treatment. For example, because an inhibitor of miR-489 promotes MSC differentiation towards the osteogenic cell fate, then this suggests that individuals with a high level of expression of miR-489 may have a reduced degree of MSC differentiation compared to individuals with a relatively lower level of miR-489 expression. Conversely, because a mimic of miR-148b promotes MSC differentiation towards the osteogenic cell fate, then this suggests that individuals with a high level of expression of miR-148b may have a higher degree of MSC differentiation compared to individuals with a relatively lower level of miR-489 expression. In one embodiment, the method comprises the steps of 1) determining the expression level of one or more of the miRNAs of the disclosure from an individual suspected of having a disease or disorder characterized by abnormal MSC differentiation (e.g., osteogenesis imperfecta) and 2) comparing the level of the one or more miRNAs with that observed in a normal individual known to not have the disease or disorder, whereby diagnostic or prognostic information may be obtained.

The miRNAs used as diagnostic or prognostic markers may be utilized individually or in combination with other molecular markers for bone disorders, including without limitation other miRNAs, mRNAs, proteins, and nucleotide polymorphisms.

A range of techniques well known in the art can be used to quantitate amounts of one or more miRNA sequences of the disclosure from e.g., a biological sample. For instance, complements of the mature miRNA sequences of the disclosure can be associated with a solid support (e.g., a microarray) and purified RNA from e.g., clinical or control samples can be fluorescently labeled and profiled to determine whether the patient is suffering from a disease resulting from improper osteogenic differentiation (see Baskerville, S. et al. RNA 11:241-7). One preferred microarray platform is described in the document in WO/2008/048342 (filed as PCT/US2007/003116) which is incorporated herein by reference in its entirety. Alternatively, Northern blotting and/or quantitative PCR-based techniques can be used to assess the relative amounts of any of the miRNAs of the disclosure derived from e.g., control and/or test samples (Duncan, D. D. et al. 2006 Anal. Biochem. 359:268-70). In addition, affinity matrices, in situ hybridization, and in situ PCR may be used. These techniques are all well known in the art.

Preferably, statistical methods are used to identify significant changes in miRNA levels for the aforementioned prognostic and diagnostic assays. For example, in one embodiment, p values are calculated using known methods to determine the significance in the change of the level of expression of a miRNA. In some embodiments, a value of p<0.05 is used as a threshold value for significance.

Samples for the prognostic and diagnostic assays of the disclosure may be obtained from an individual (e.g., a human or animal subject) suspected of having a disease or disorder characterized by abnormal MSC differentiation (e.g., osteogenesis imperfecta) using any technique known in the art. For example, the sample may be obtained from an individual who is manifesting clinical symptoms that are consistent with the existence of a disease or disorder characterized by abnormal MSC differentiation, or from an individual with no clinical symptoms but with a predisposition towards developing a disease or disorder characterized by abnormal MSC differentiation due to genetic or environmental factors. Samples may be obtained by extracting a small portion of bone tissue from an individual using, for example, a biopsy needle.

In some instances, genomic amplification of a sequence encoding a miRNA in a tissue may result in a higher level of expression of that miRNA relative to tissues in which the sequence encoding the miRNA has not undergone amplification. Thus, in another embodiment, the copy number of miR-489, miR-27a, and miR-148b is measured in a tissue which comprises MSCs. Methods suitable for determining the genomic copy number of a sequence encoding a miRNA include Southern blotting, fluorescence in situ hybridization, comparative genomic hybridization, and amplification based methods such as quantitative PCR (for example, using Taqman probes).

The methods of the disclosure can also be used to identify genes that play a role in enhancing osteogenesis and/or limit MSC differentiation into other cell types (e.g. adipocytes). The terms “miRNA target gene”, “miRNA target”, and “target gene” are used interchangeably herein to refer to genes that are directly modulated by specific miRNA(s). Extensive studies into the mechanism of miRNA action have identified characteristic features of miRNA target genes. These include the presence of the 3′ UTR target sites (e.g. seed complements), the number and positioning of seed complements within a 3′ UTR, preferences for local AU-rich sequences and more (see, for instance, Grimson, A. et al 2007. Mol Cell 27:91-105). As such, miRNA target genes can be identified bioinformatically (e.g., see the miRNA target prediction site at the http site on the world-wide-web: russell.embl-heidelberg.de/miRNAs; Targetscan, the http site on the world-wide-web: targetscan.org/mam_(—)31/), by microarray analysis (Huang et. al., 2007, Nature Methods 4:1045-9), and by biochemical methods (Karginov, F. V., 2007, PNAS 104:19291-6). Using the procedures described in Example 5, the inventors have determined target genes that are regulated by miRs-27a, 489, and 148b, including but not limited to the target genes disclosed in Tables 2-7. Thus, in another aspect, the disclosure provides a collection of target genes that are modulated by miRs-27a, 489, and 148b, including the genes in Tables 2-7. The nucleotide sequences of the genes in Tables 2-7 are well known in the art. For example, gene sequences may be obtained through http site//www.ncbi.nlm.nih.gov/sites/entrez?db=gene using the gene names, target names, Transcript Id. Numbers and ReqSeq Accession Numbers provided in Tables 2-7. For each gene of Tables 2-7, the most recent version of the sequence associated with the recited accession number as of the filing date of this application is specifically incorporated herein by reference.

It will be recognized by one skilled in the art that knowledge of the target genes that are modulated by miRs-27a, 489, and 148b enables other methods for modulating mesenchymal stem cell differentiation both ex vivo (e.g. in vitro) and in vivo. In general, a decrease in the expression level of a gene from Tables 2-3 or Tables 4-5 (e.g. CHRD, GCA, and SLC22A2) will inhibit mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate, whereas an increase in the expression level of a gene from Tables 2-3 or Tables 4-5 will promote mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate. Similarly, a decrease in the expression level of a gene from Tables 6-7 (e.g. NOG) will promote mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate, whereas an increase in the expression level of a gene from Tables 6-7 will inhibit mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate.

In addition to using the miRNAs, miRNA mimics, and miRNA inhibitors disclosed above, modulation of the expression level of the target genes provided in Tables 2-7 can also be achieved using miRNA mimics that hybridize to a different site in the target gene than the site recognized by the endogenous miRs-27a, 489, and 148b.

Modulation of the expression level of the target genes provide in Tables 2-7 can also be achieved using siRNAs that can be designed using techniques well known in the art. Non-limiting examples demonstrating the siRNA-mediated modulation of the target genes of Tables 2-7 are provided in Example 5. For example, in one embodiment, the disclosure provides a method of promoting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate, the method comprising introducing into a MSC at least one siRNA or miRNA mimic specific for at least one of the target genes of Tables 6-7 (e.g. a siRNA specific for NOG). In another embodiment, the disclosure provides a method of inhibiting mesenchymal stem cell (MSC) differentiation towards the osteogenic cell fate, the method comprising introducing into a MSC at least one siRNA or miRNA mimic specific for at least one of the target genes of Tables 2-5 (e.g. CHRD, GCA, and SLC22A2). In preferred embodiments, the expression level of one or more genes from Table 3, 5, and/or 7 (e.g. ARSE, COL2A1, FBN1, GHRHR, HOXA2, HOXA5, LECT1, NOG, OSTF1, PAPSS2, TFIP11, TRPS1, ADAMTS4, AHSG, ALPL, BMI1, CHRD, DLX5, HOXA13, MATN1, MINPP1, PEX7, PRKRA, THRA, AMELY, BMP7, CDH11, CHRD, CHRDL2, EN1, MAPK8, MGP, PAX1, POSTN, SPP1, SUFU, TRAPPC2, TWIST1, GCA, and SLC22A2) is modulated in an MSC in vivo or ex vivo (e.g. in vitro) using miRNAs, miRNA mimics, miRNA inhibitors, siRNA, and/or any other mediator of RNAi or transcriptional silencing known in the art.

It is expressly contemplated that combinations of two or more agents of the disclosure (miRNAs, miRNA mimics, miRNA inhibitors, and siRNAs) are used to modulate MSC differentiation in vivo or ex vivo.

The identification of the target genes of Tables 2-7 that are induced and/or suppressed by the miRNA mimics and inhibitors described herein can also lead to the identification of small molecules that can modulate this critical step in cellular differentiation. Small molecules can be identified, for example, using conventional High Throughput Screening (HTS) methodology.

All of the agents identified in the instant disclosure (miRNAs, miRNA mimics, miRNA inhibitors, and siRNAs) that modulate MSC differentiation have utility in the fields of tissue transplantation/grafting (e.g. bone formation, tissue mineralization, osteochondrial repair, fracture repair including non-union fracture repair), treatment of disease (e.g. osteogenesis imperfecta), bioprocessing, 3D culture, and biomarker development (see, for instance, Reiker, J. et al. (2005) Expert Opin. Biol. Ther. 5(12): 1572-1584). For example, using a differentiation promoting agent(s) of the disclosure (e.g., a miR-148b mimic, a miR-489 inhibitor, a miR-27a inhibitor, or siRNA or an miRNA mimic specific for a gene from Tables 6-7, such as NOG, or any combination of two or more of these agents such as two miR-489 inhibitors, or such as a miR-489 inhibitor plus a siRNA specific for NOG, or such as a miR-27a inhibitor plus a miRNA mimic for NOG etc), a MSC cultured ex vivo may be induced to differentiate towards the osteogenic cell fate and may then be transplanted into an individual in need of a bone graft along with an appropriate matrix or implant, if required. The MSC may be obtained from the same individual that receives the bone graft (autograft) or from a different individual (allograft).

Pharmaceutical compositions comprising the inhibitors, mimics, siRNAs, and small molecules of the disclosure, are also expressly contemplated and may be used for the treatment (e.g. therapy—ranging from alleviation of one or more symptoms to a complete cure—or prophylaxis) of any disease, condition, or disorder in which MSC differentiation (or lack thereof) is implicated (e.g. osteogenesis imperfecta) or where increased osteogenesis is desirable (e.g. osteoporosis or any other disease, condition, or disorder where increasing bone density and growth is desirable such as, without limitation, osteoarthritis, periodontal disease, bone fractures of any type or etiology, bone loss from surgery, reconstructive surgery, osteomylitis, and idiopathic bone loss) or where decreased osteogenesis is desirable (e.g. fibrodysplasia ossificans progressiva). For example, a pharmaceutical formulation comprising at least one siRNA or miRNA mimic specific for a gene from Tables 6-7 (e.g. NOG) can be used to treat an individual suffering from a disease characterized by a decreased degree of MSC differentiation relative to a normal individual, or to treat a disease or disorder in which increasing bone growth, mass, or density is desirable. Similarly, a pharmaceutical formulation comprising at least one siRNA or miRNA mimic specific for a gene from Tables 2-5 (e.g. CHRD, GCA, and SLC22A2) can be used to treat an individual suffering from a disease characterized by a increased degree of MSC differentiation relative to a normal individual. Preferably, the target gene whose expression level is modulated by a siRNA or miRNA mimic is a gene from Table 3, 5, or 7. By way of another example, a pharmaceutical formulation comprising at least one miR-148b mimic and/or at least one miR-489 inhibitor and/or at least one miR-27a inhibitor and/or at least one siRNA specific for a gene from Tables 6-7 can be used to treat an individual suffering from a disease characterized by a decreased degree of MSC differentiation relative to a normal individual. By way of another example, a pharmaceutical formulation comprising at least one miR-489 mimic and/or least one miR-27a mimic and/or at least one miR-148b inhibitor and/or at least one siRNA specific for a gene from Tables 2-5 can be used to treat an individual suffering from a disease characterized by a increased degree of MSC differentiation relative to a normal individual. In all cases, a pharmaceutically effective amount of the composition is administered to an individual in need thereof, such as a human patient i.e. an amount that is sufficient to induce a response in the individual that is clinically relevant and significant.

In addition to the siRNA(s), miRNA mimic(s), and miRNA inhibitor(s), the pharmaceutical formulations preferably also comprise one or more pharmaceutically acceptable carriers or excipients, and may be formulated for a variety of routes of administration, including systemic and topical or localized administration. Techniques and formulations generally may be found in Remmington's Pharmaceutical Sciences, Meade Publishing Co., Easton, Pa. For systemic administration, injection is preferred, including intramuscular, intravenous, intraperitoneal, and subcutaneous. For injection, the therapeutic compositions of the invention can be formulated in liquid solutions; preferably in physiologically compatible buffers such as Hank's solution or Ringer's solution. In addition, the therapeutic compositions may be formulated in solid form and redissolved or suspended immediately prior to use. Lyophilized forms are also included. Preparations for oral administration are also contemplated, and may be formulated in a conventional manner to give either immediate or controlled release.

The pharmaceutical compositions of the disclosure may also include an additional active ingredient(s) for the treatment of bone disease e.g. TAK-778 R2R,4S)-(−)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide.

In another aspect, the level of expression of one or more of the target genes of Tables 2-7 is measured. The results of measurements can be used for disease detection, disease diagnosis, disease prognosis, and to determine or predict the efficacy of a therapeutic treatment. For example, individuals with a high level of expression of a gene from Tables 6-7 (e.g. NOG) may have a reduced degree of MSC differentiation compared to individuals with a relatively lower level of expression of the same gene(s). Conversely, individuals with a low level of expression of a gene from Tables 6-7 may have a higher degree of MSC differentiation compared to individuals with a relatively higher level of expression of the same genes. Similarly, individuals with a high level of expression of a gene from Tables 2-5 (e.g. CHRD, GCA, SLC22A2) may have a higher degree of MSC differentiation compared to individuals with a relatively lower level of expression of the same gene(s); individuals with a low level of expression of a gene from Tables 2-5 may have a reduced degree of MSC differentiation compared to individuals with a relatively higher level of expression of the same gene(s). Methods for the measurement of the expression level of the target genes of Table 2-7 are well-known in the art, and include Northern blotting and quantitative PCR-based methods and microarray analysis (see also the methods disclosed above for measuring miRNA levels which are generally applicable to the measurement of mRNA also). In other embodiments, the level of the protein encoded by a gene from Tables 2-7 is measured using, for example, western blots, antibody arrays, ELISA assays, or any other technique known in the art.

The assays can be performed on biological samples taken from the individual. In one embodiment, the method comprises the steps of 1) determining the expression level of one or more of the target genes of Tables 2-7 from an individual suspected of having a disease or disorder characterized by abnormal MSC differentiation (e.g., osteogenesis imperfecta) and 2) comparing the level of the one or more target genes with that observed in a normal individual known to not have the disease or disorder, whereby diagnostic or prognostic information may be obtained. Preferably, the target gene whose expression level is determined is a gene from Table 3, 5, or 7 (e.g. ARSE, COL2A1, FBN1, GHRHR, HOXA2, HOXA5, LECT1, NOG, OSTF1, PAPSS2, TFIP11, TRPS1, ADAMTS4, AHSG, ALPL, BMI1, CHRD, DLX5, HOXA13, MATN1, MINPP1, PEX7, PRKRA, THRA, AMELY, BMP7, CDH11, CHRD, CHRDL2, EN1, MAPK8, MGP, PAX1, POSTN, SPP1, SUFU, TRAPPC2, TWIST1, GCA, and SLC22A2). The targets genes of Tables 2-7 may be used as diagnostic or prognostic markers either individually or in combination with other molecular markers disclosed herein or identified in previous or future studies (e.g., other miRNAs, proteins, nucleotide polymorphisms).

In another embodiment, the miRNAs and target genes described herein can be used as molecular markers in drug screening assays during drug development. Typically, in the early stages of drug development, in vitro studies involving cultured cells that often mimic one or more aspects of diseased tissue are performed to identify molecules that induce desirable phenotypes. As up or down regulation of miRNAs or target genes described herein are indicative of e.g. osteogenic differentiation, they can be used as markers during drug development to identify agents that positively effect clinical outcomes. In one preferred example, one or more of the miRNAs described herein are used to screen a collection of small molecules to identify agents that modulate the expression of the target gene sequences listed in the enclosed tables. Agents that cause e.g., miRNA(s) expression levels to return to a level that is more normal would be considered potential therapeutic candidates.

In another example, one or more of the miRNAs described herein are used as prognostic indicators to judge the effectiveness of drug treatment regimes. For example, the levels of miRNAs of the disclosure can be assessed in osteogenesis imperfecta patients receiving a particular treatment to determine the effectiveness of the treatment in lessening one or more phenotypes of the disease.

In another aspect, an exogenous vector construct comprising at least part of the coding sequence of a gene from Tables 2-7 is expressed in cells ex vivo or in vivo in order to modulate MSC differentiation. For example, in one embodiment, MSC differentiation towards the osteogenic cell fate is promoted by expressing an expression construct comprising at least part of the coding sequence of a gene from Tables 2-5 (e.g. at least part of the coding sequence of CHRD, GCA, or SLC22A2) operationally linked to sequences that allow the expression of the coding sequence. In another embodiment, MSC differentiation towards the osteogenic cell fate is inhibited by expressing an expression construct comprising at least part of the coding sequence of a gene from Tables 6-7 (e.g. at least part of the coding sequence of NOG) operationally linked to sequences that allow the expression of the coding sequence. Methods for generating and expressing expression constructs, including methods for expressing such constructs in vivo in humans, are well known in the art.

The aforementioned treatment and diagnostic methods are preferably carried out using human subjects; however, one skilled in the art will recognize that the methods of the disclosure can also be carried out in other animal species which possess orthologs of the genes of the Table 2-7 and/or of miR-148b, miR-489, and miR-27a. Determining orthologs of the genes and miRs of the disclosure in other animal species is within the skill of the ordinary worker in the field.

Note that while the invention has been described with reference to the differentiation of MSCs, the inventors have also recognized that the methods and agents provided herein may be used to modulate the differentiation of any other cell type that has osteogenic potential. Thus, in another series of embodiments, the disclosure provides methods of promoting differentiation towards the osteogenic cell fate of a cell having osteogenic potential, the methods comprising introducing into the cell (in vivo or ex vivo) an effective amount of a composition comprising at least one differentiation promoting agent selected from the group consisting of inhibitors of miR-489, inhibitors of miR-27a, mimics of miR-148b, and siRNAs specific for genes from Tables 6-7. Similarly, in another series of embodiments, the disclosure provides methods of inhibiting differentiation towards the osteogenic cell fate of a cell having osteogenic potential, the methods comprising introducing into the cell (in vivo or ex vivo) an effective amount of a composition comprising at least one differentiation inhibitor selected from the group consisting of mimics of miR-489, mimics of miR-27a, siRNAs specific for genes from Tables 2-5, and inhibitors of miR-148b.

Given the general applicability of the methods and agents of the disclosure in modulating the differentiation of cells having osteogenic potential (not just MSCs), it will be clear that any disease or condition that is characterized by either inadequate or inappropriate osteogenesis (e.g. ectopic osteogenesis or increased osteogenesis) may be treated using the methods and agents of the disclosure i.e. the methods of the disclosure are not restricted to the treatment of diseases or conditions in which MSC differentiation (or lack thereof) plays a pathological role. Similarly, using the diagnostic methods disclosed herein, diagnostic and prognostic information may be obtained regarding any disease or condition characterized by either inadequate or inappropriate osteogenesis (e.g. ectopic osteogenesis or increased osteogenesis) i.e. the diagnostic methods of the disclosure are not restricted to the diagnosis of diseases or conditions in which MSC differentiation (or lack thereof) plays a pathological role.

By way of non-limiting example, it is known that certain vascular cells, namely vascular smooth muscle cells (VSMS), calcifying vascular cells (CVC), and pericytes have the ability to differentiate into osteoblasts (or osteoblast-type cell). With respect to VSMCs, it is known that these cells have the ability to differentiate into osteoblasts (or osteoblast-type cell) in response to several stimuli including oxidative stress, bone morphogenetic proteins, or changes in pyrophosphate levels. It has been suggested that the ability of VSMSs, CVCs, and/or pericytes to differentiate into osteoblasts may explain the development of vascular calcifications, such as atherosclerotic calcification, medial artery calcification, and cardiac valve calcification. Johnson et al., Circulation Research 99:1044-1059 (2006). Thus, the methods and agents of the disclosure may be used in the treatment or prevention of vascular calcification. In particular, the agents of the disclosure that inhibit the differentiation towards the osteogenic cell fate of cells having osteogenic differentiation potential (mimics of miR-489, mimics of miR-27a, siRNA specific for genes from Tables 2-5, and inhibitors of miR-148b) may be administered (e.g. in pharmaceutical compositions) to a patient to treat or prevent vascular calcification.

The following examples are non-limiting.

EXAMPLES

General Reagents and Techniques

Mesenchymal stem cells, propagation media, and differentiation media were obtained from Lonza, Inc (Basel, Switzerland). Total alkaline phosphatase was determined using an osteogenesis assay kit from Biomedical Research Service Center (SUNY, Buffalo, N.Y.). To detect alkaline phosphatase expression in individual cells, ELF kits were purchased from ATCC (Manassas, Va.). Cells were then analyzed for alkaline phosphatase activity using an ArrayScan VTi (Thermo Fisher).

In most assays, cells (2,500 cells per well, 96 well plate) were transfected with miRNA mimics and inhibitors (25 nM, DharmaFECT1 Lipid) and incubated for approximately six days before assessing the level of osteogenic differentiation.

Example 1

Primary Screen for microRNAs that Alter MSC Differentiation Using miRNA Inhibitors

To identify microRNAs that play an important role in MSC osteogenic differentiation, a screen using microRNA inhibitors targeting over 400 human miRNAs (miR database) was performed in adult human mesenchymal stem cells. To achieve this, MSC cells (Lonza, Inc) were plated in propagation media (Lonza, Inc) at a density of 2.5K cells per well in a 96-well plate (Nunc). At t=24 h, cells were transfected with miRNA inhibitors (miRIDIAN inhibitors, Thermo Fisher Scientific, 25 nM) and cultured for 6 days in differentiation media (Lonza, Inc). Subsequently, cells were lysed, the level of alkaline phosphatase (a classic osteogenic marker) was measured (osteogenesis assay kit, Biomedical Research Service Center, Cat # A-104) and normalized to total protein to determine the relative level of alkaline phosphatase expression in each culture. Untreated cells, cells treated with a negative control inhibitor (5′ mAmGmCmUmCmUmCmAmUm CmCmAmUmGmGmAmUmCmUmAmCmUmCmUmUmUmCmUmAmGmGmAmGm GmUmUmGmUmGmAmUmGmGmUmAmCmCmUmAmCmUmCmUmCmGmA, fully 2′-O-methylated, inhibitor of C. elegans miR-67) (SEQ ID NO:1), and cells treated with siRNA targeting the RUNX2 transcription factor which has been identified as being important in MSC cell differentiation into osteocytes were used as controls in the primary screen. Results were assessed using Excel software (Microsoft, Inc.) and standard statistical tools common to the art (e.g. z score).

Results of these experiments are presented in FIG. 1. While the majority of inhibitors failed to significantly alter the level of osteogenic differentiation in the culture, a subset (including all of the miRNA inhibitors listed in Table 1) had significant effects on the expression levels of alkaline phosphatase. In particular, transfection of cells with inhibitors targeting hsa-miR-489 and hsa-miR-27a increased alkaline phosphatase levels by as much as 300% over control (non-targeting) miRNA inhibitors. In contrast, treating the cells with inhibitors to hsa-miR148b decreased alkaline phosphatase levels by approximately two-fold (as compared to inhibitor control molecules). These results were confirmed with a second inhibitor design that utilized hairpin flanking regions to enhance functionality of the molecule.

TABLE 1 Lists of miRNAs that when targeted with an inhibitor  molecule, increase or decrease MSC osteogenic  differentiation. The identity of the miRNA, as well as the sequence of the inhibitor and mimic   used in the experiments described in this document are provided. Sequence: “m” = methylated, “p” = phosphorylated. All sequences  Molecule reported as 5′→3′ SEQ ID NO: hsa-miR-489 mAmGmCmUmCmUmGmAmAmAmAmG 2 inhibitor mAmGmCmUmGmCmUmGmCmCmGmUm AmUmAmUmGmUmGmAmUmGmUmCm AmCmUmUmCmGmAmGmAmUmUmCmG mUmCmUmCmGmA hsa-miR-489 pUCAGUGCAUCACAGAACUUUGU 3 mimic sequence (AS strand) hsa-miR-489 mUmGCCGUAUAUGUGAUGUCACU 4 mimic sequence (S strand) hsa-miR-148b mAmGmCmUmCmUmCmAmUmCmCmAm 5 inhibitor UmGmGmAmGmAmCmAmAmAmGmUm UmCmUmGmUmGmAmUmGmCmAmCmU mGmAmCmUmUmGmUmAmCmCmUmA mCmUmCmUmCmGmA hsa-miR-148b pUCAGUGCAUCACAGAACUUUGU 6 mimic (AS strand) hsa-miR-148b mAmAAGUUCUGUGAUGCACUGAUU 7 mimic (S strand) hsa-miR-27a mAmGmCmUmCmUmCmAmUmCmCmAm 8 inhibitor UmGmGmGmGmGmGmCmGmGmAmAm CmUmUmAmGmCmCznAmCmUmGmUmG mAmAmCznAmCmGmUmAmCmCmUmAm CmUmCmUmCmGmA hsa-miR-27a pUUCACAGUGGCUAAGLTUCCGC 9 mimic (AS strand) hsa-miR-27a mGmGAACUUAGCCACUGUGAAUU 10 mimic (S strand) Control  mAmGmCmUmCmUmCmAmUmCmCmAm 11 inhibitor UmGmGmAmUmCmUmAmCmUmCmUmU mUmCmUmAmGmGmAmGmGmUmUmG mUmGmAmUmGmGmUmAmCmCmUmA mCmUmCmUmCmGmA Control mimic pUCACAACCUCCUAGAAAGAGUAGA 12 (AS strand) Control mimic mUmACUCUUUCUAGGAGGUUGUGAUU 13 (S strand)

Example 2

Test of microRNA Mimics in MSC Differentiation

If an miRNA inhibitor increases differentiation, it was predicted that a miRNA mimic of the same microRNA would decrease differentiation. Conversely, if an miRNA inhibitor decreased differentiation, it was predicted that treatment of cells with the mimic for that miRNA would amplify differentiation. To that end, miRNA mimics that corresponded to the positive hits observed in the primary (inhibitor) screen were synthesized and transfected into MSCs (2.5K cells per well, 25 nM miRNA mimic, Thermo Fisher Scientific).

Only three of the miRNAs identified in the primary inhibitor screen exhibited the predicted effects in the mimic screen (see Table 1). While transfection of cells with inhibitors targeting hsa-miR-489 and hsa-miR-27a increased alkaline phosphatase levels, introduction of the corresponding mimics significantly decreased overall differentiation (see FIG. 2 a). While treating the cells with inhibitors to hsa-miR148b decreased alkaline phosphatase levels, treatment with the corresponding mimic induced the opposite phenotype, elevating alkaline phosphatase expression by over 800%. Both inhibitor and mimic results were dose-dependent (see FIGS. 2B-G). These results indicate that hsa-miR-489, hsa-miR-27a, and hsa-miR148b play a role in MSCs osteogenic differentiation and that mimics and inhibitors for these miRNAs can be used to modulate differentiation.

Example 3

Identification of Combinations of miRNA Inhibitors and/or Mimics that Provide Additive Effects.

Transfection of 1) hsa-miR-489 inhibitors, 2) hsa-miR-27a inhibitors, or 3) hsa-miR148b mimics enhanced expression of alkaline phosphatase and thus osteogenic differentiation by MSCs. To determine whether any combination of these reagents acted in an additive fashion, the action of individual inhibitor or mimic molecules (e.g. inhibitor 489, inhibitor 27a, or mimic 148b) was compared with various combinations including 1) i489+i27a, 2) i489+m148b, 3) i27a+m148b, and 4) i489+i27a+m148b in the differentiation assay. To achieve this, MCS cells were plated at standard cell densities (2.5K per well, standard propagation media) and either individual, pairs, or trios of inhibitors, or inhibitors and mimics were transfected. In this instance, alkaline phosphatase expression was assessed on a cell-by-cell basis using an ELF kit purchased from ATCC (Cat. # SCRR-3010). Briefly, following transfection, cells were incubated in propagation media for 6 days and then fixed in 4% paraformaldehyde. Subsequently, cultures were stained with ELF97 fluorogenic substrate to detect alkaline phosphatase, and counterstained with SYTO Green to label nuclei. Cells were then analyzed for alkaline phosphatase activity using an ArrayScan VTi (Thermo Fisher).

The results of these experiments along with the appropriate controls are presented in FIG. 3A. Only two combinations (i489+m148b and i489+i27a+m148b) significantly enhanced the expression of alkaline phosphatase (and thus osteogenic differentiation.) in this assay. As a single pairing (i489+m148b) is common in both data sets, this indicates that the i489+m148b combination acts additively to enhance osteogenic differentiation by MSCs.

Example 4

miRNA Inhibitors and Mimics Induce Differentiation in Standard Propagation Media

Initial studies designed to identify miRNA inhibitors and mimics that enhanced osteogenic differentiation were performed in differentiation media. To determine whether the inhibitors and mimics identified in Examples 1 and 2 could induce their effects in propagation media, differentiation studies were performed in both differentiation media and standard propagation media (Lonzo Biologics, Inc).

The results of these experiments are presented in FIGS. 3A and 3B, which show that hsa-miR-489, and hsa-miR-27a inhibitors, as well as hsa-miR148b mimics induce alkaline phosphatase expression in both media conditions. This finding indicates that the inhibitors and mimics listed induce MSC osteogenic differentiation in the absence of other signals.

Example 5

Identifying Targets of miRs-27a, 489, and 148b.

To identify targets of the preferred miRNAs identified in previous examples, the sequence of each miRNA was entered into miRanda (the http site: //www.mircoma.org/microrna/home.do) and a list of potential targets was generated based on the presence of 3′ UTR seed complements and additional parameters (see, Lewis et al, (2005) Cell, 120:15-20). For miR-27a, 956 target genes were predicted, for miR-489, 888 target genes, and 327 target genes were predicted for miR-148b. See Tables 2, 4, and 6. Interestingly, roughly 80 of the bioinformatically identified targets were common to both miR-27a and miR-489, the two miRNAs that when introduced into MSCs, inhibited osteogenic differentiation. Additional in silico techniques were then employed to further narrow the list of targets provided by miRanda. Specifically, the genes identified by miRanda were analyzed using the gene ontology tool L2L (the http site: //depts.washington.edu/121/database.html) to identify members that were associated with “skeletal development”. From this study, 15 of the 956 target genes initially identified for miR-27a, 12 of the 888 target genes for miR-489, and 12 of the 827 target genes for miR-148b were identified (see Tables 3, 5, and 7).

In order to confirm the target genes identified herein are indeed functionally linked with the miRNAs identified, siRNAs were developed to a subset of the selected target genes to assess the involvement of the gene in osteogenic differentiation. We predicted that if these genes are truly targets of the respective miRNAs, then knockdown of those genes by siRNAs should mimic the effects of the respective miRNA. Four genes exemplified below represent this scenario; three that were predicted to be targeted by both miR-27a and miR-489 and one that was predicted to be targeted by miR-148b.

For these experiments, pools of siRNAs targeting NOG, CHRD, GCA, SLC22A2, RUNX2 (a positive control), or a non-targeting siRNA (a negative control, “control siRNA”) were introduced into hMSCs. Cells were then transferred to differentiation media (48 hr after transfection) and assessed for the expression of AP 6 days after osteogenic induction.

The results of these studies are presented in FIG. 4 and demonstrate that knockdown of the respective targets mimics the phenotypes associated with the respective miRNAs. Specifically, in cultures treated with siRNA targeting CHRD, GCA and SLC22A2, expression of AP was similar to that observed in cultures where RUNX2 (a known modulator of osteogenic differentiation) was targeted (i.e. less than 50% of the controls). This phenotype is similar to that induced by miR-27a and miR-489 which are predicted to target the CHRD, GCA and SLC22A2 gene. In contrast, cultures treated with siRNA targeting NOG exhibited AP levels that were 2.5 times those observed in control (non-targeting siRNA) cultures. Again, this phenotype parallels that observed when cells were treated with miR148b, the miRNA that targets NOG. Together these studies validate 1) the function of miRs-27a, 489, and 148b in their role as regulators of osteogenic differentiation, and 2) the methods used to identify targets of the preferred miRNAs.

Tables 2, 4, and 6 represent miRNA target gene lists as determined by miRanda alone. Tables 3, 5, and 7 represent miRNA target gene lists as determined by miRanda followed by L2L bioinformatic procedures.

TABLE 2 All targets of miR-27a. RefSeq Accession Transcript ID Number Target Name Gene Name ENST00000229384 15E2_HUMAN ENST00000382381 NM_001089 ABCA3 ATP-binding cassette, sub- family A (ABC1), member 3 ENST00000375538 NM_007168 ABCA8 ATP-binding cassette, sub- family A (ABC1), member 8 ENST00000382075 NM_178559 ABCB5 ATP-binding cassette, sub- family B (MDR/TAP), member 5 ENST00000339447 ABCB7 ATP-binding cassette, sub- family B (MDR/TAP), member 7 ENST00000347800 NM_004915 ABCG1 ATP-binding cassette, sub- NM_016818.2 family G (WHITE), member 1 NM_207174 NM_207627.1 NM_207628.1 NM_207629 ENST00000360937 NM_001091.2 ABP1 Amiloride binding protein 1 (amine oxidase (copper- containing)) ENST00000285093 NM_001080467.1 ACAA2 Acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) ENST00000373695 NM_052957 ACRC Acidic repeat containing ENST00000289416 ACSM3 Acyl-CoA synthetase medium- chain family member 3 ENST00000224784 ACTA2 Actin, alpha 2, smooth muscle, aorta ENST00000188312 NM_022496 ACTR6 ARP6 actin-related protein 6 homolog (yeast) ENST00000265708 NM_001464 ADAM2 ADAM metallopeptidase domain 2 (fertilin beta) ENST00000367995 NM_005099 ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif, 4 ENST00000381052 NM_197941 ADAMTS6 ADAM metallopeptidase with thrombospondin type 1 motif, 6 ENST00000383707 NM_182920 ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 ENST00000358680 ADC Arginine decarboxylase ENST00000380823 ADCY3 Adenylate cyclase 3 ENST00000304222 ADORA2B Adenosine A2b receptor ENST00000380572 NM_000680 ADRA1A Adrenergic, alpha-1A-, receptor NM_033302 NM_033303 NM_033304 ENST00000269143 NM_006796 AFG3L2 AFG3 ATPase family gene 3-like 2 (yeast) ENST00000375826 AGMAT Agmatine ureohydrolase (agmatinase) ENST00000264167 NM_003659 AGPS Alkylglycerone phosphate synthase ENST00000273784 NM_001622 AHSG Alpha-2-HS-glycoprotein ENST00000375341 NM_003748 ALDH4A1 Aldehyde dehydrogenase 4 NM_170726 family, member A1 ENST00000302708 ALKBH3 AlkB, alkylation repair homolog 3 (E. coli) ENST00000374832 NM_000478 ALPL Alkaline phosphatase, liver/bone/kidney ENST00000330330 AMY2B Amylase, alpha 2B (pancreatic) ENST00000255667 NM_032290 ANKRD32 Ankyrin repeat domain 32 ENST00000265224 ANKRD7 ENST00000375109 ANP32B Acidic (leucine-rich) nuclear phosphoprotein 32 family, member B ENST00000374368 NM_174890 ANUBL1 AN1, ubiquitin-like, homolog (Xenopus laevis) ENST00000296511 NM_001154 ANXA5 Annexin A5 ENST00000258749 NM_001637 AOAH Acyloxyacyl hydrolase (neutrophil) ENST00000246149 NM_015013 AOF2 Amine oxidase (flavin containing) domain 2 ENST00000346661 NM_007247 AP1GBP1 AP1 gamma subunit binding NM_080550 protein 1 ENST00000359032 NM_014203.2 AP2A1 Adaptor-related protein complex NM_130787.2 2, alpha 1 subunit ENST00000316757 APBA3 Amyloid beta (A4) precursor protein-binding, family A, member 3 (X11-like 2) ENST00000355285 NM_153000 APCDD1 Adenomatosis polyposis coli down-regulated 1 ENST00000257254 APJ_HUMAN ENST00000244669 NM_006789 APOBEC2 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide- like 2 ENST00000313578 NM_173039 AQP11 Aquaporin 11 ENST00000320481 NM_020824 ARHGAP21 Rho GTPase activating protein 21 ENST00000374872 NM_015185 ARHGEF9 Cdc42 guanine nucleotide exchange factor (GEF) 9 ENST00000320767 NM_025047 ARL14 ADP-ribosylation factor-like 14 ENST00000379532 ARMC6_HUMAN ENST00000263634 NM_016115 ASB3 Ankyrin repeat and SOCS box- NM_145863 containing 3 ENST00000380920 NM_001671 ASGR1 Asialoglycoprotein receptor 1 ENST00000215906 ASPHD2 Aspartate beta-hydroxylase domain containing 2 ENST00000372393 ASS ENST00000378759 ATAD3A ATPase family, AAA domain containing 3A ENST00000378737 ATAD3B ATPase family, AAA domain containing 3B ENST00000373673 NM_145178 ATOH7 Atonal homolog 7 (Drosophila) ENST00000218008 NM_012069 ATP1B4 ATPase, (Na+)/K+ transporting, beta 4 polypeptide ENST00000284727 NM_001002258 ATP5G3 ATP synthase, H+ transporting, NM_001689 mitochondrial F0 complex, subunit C3 (subunit 9) ENST00000369762 NM_001183 ATP6AP1 ATPase, H+ transporting, lysosomal accessory protein 1 ENST00000264649 ATP6V0A1 ATPase, H+ transporting, lysosomal V0 subunit a1 ENST00000374133 ATPBD1B ATP binding domain 1 family, member B ENST00000270637 ATPBD3 ATP binding domain 3 ENST00000378853 AURKAIP1 Aurora kinase A interacting protein 1 ENST00000358927 NM_000054 AVPR2 Arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) ENST00000320865 B3GNTL1 UDP-GlcNAc:betaGal beta-1,3- N- acetylglucosaminyltransferase- like 1 ENST00000367998 B4GALT3 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 3 ENST00000370693 NM_004282 BAG2 BCL2-associated athanogene 2 ENST00000286639 NM_006399 BATF Basic leucine zipper transcription factor, ATF-like ENST00000359924 BBC3_HUMAN ENST00000371608 BCAS4 Breast carcinoma amplified sequence 4 ENST00000310512 BCDIN3 ENST00000164227 NM_005178 BCL3 B-cell CLL/lymphoma 3 ENST00000361907 NM_017745 BCOR BCL6 co-repressor NM_020926 ENST00000372677 BEX2 Brain expressed X-linked 2 ENST00000372645 BEX3_HUMAN ENST00000376719 NM_005180 BMI1 BMI1 polycomb ring finger oncogene ENST00000368636 BNIP3 BCL2/adenovirus E1B 19 kDa interacting protein 3 ENST00000336049 NM_033030 BOLL Bol, boule-like (Drosophila) NM_197970 ENST00000382392 NM_001002760.1 BPY2C Basic charge, Y-linked, 2C NM_001002761.1 NM_004678.1 ENST00000324096 BPY2IP1 ENST00000303498 NM_000060 BTD Biotinidase ENST00000290551 NM_006763 BTG2 BTG family, member 2 ENST00000368859 BUB3 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast) ENST00000222969 BUD31 BUD31 homolog (S. cerevisiae) ENST00000370654 BXDC5 Brix domain containing 5 ENST00000372996 BYSL Bystin-like ENST00000369286 NM_018017 C10orf118 Chromosome 10 open reading frame 118 ENST00000368815 NM_015608 C10orf137 Chromosome 10 open reading frame 137 ENST00000378605 C10orf30 Chromosome 10 open reading frame 30 ENST00000373279 NM_145306 C10orf35 Chromosome 10 open reading frame 35 ENST00000278064 NM_025145 C10orf79 Chromosome 10 open reading frame 79 ENST00000264020 NM_020153 C11orf60 Chromosome 11 open reading frame 60 ENST00000381047 NM_018169 C12orf35 Chromosome 12 open reading frame 35 ENST00000305457 NM_152335 C15orf27 Chromosome 15 open reading frame 27 ENST00000268138 NM_152259 C15orf42 Chromosome 15 open reading frame 42 ENST00000340827 NM_152448 C15orf43 Chromosome 15 open reading frame 43 ENST00000329410 NM_175900 C16orf54 Chromosome 16 open reading frame 54 ENST00000323355 NM_152728 C18orf20 Chromosome 18 open reading frame 20 ENST00000382462 C19orf24 Chromosome 19 open reading frame 24 ENST00000317292 C19orf30 Chromosome 19 open reading frame 30 ENST00000374526 NM_020362 C1orf128 Chromosome 1 open reading frame 128 ENST00000371007 NM_001013674 C1orf141 Chromosome 1 open reading frame 141 ENST00000366760 C1orf142 Chromosome 1 open reading frame 142 ENST00000370574 NM_017953 C1orf181 Chromosome 1 open reading frame 181 ENST00000367974 C1orf192 Chromosome 1 open reading frame 192 ENST00000368369 NM_006589 C1orf2 Chromosome 1 open reading NM_198264 frame 2 ENST00000369095 NM_018997 C1orf51 Chromosome 1 open reading NM_031901 frame 51 NM_144697 ENST00000366628 C1orf57 Chromosome 1 open reading frame 57 ENST00000367723 NM_014283 C1orf9 Chromosome 1 open reading NM_016227.1 frame 9 ENST00000251071 C1QDC1 ENST00000304189 C20orf55 ENST00000370351 C20orf59 Chromosome 20 open reading frame 59 ENST00000354932 NM_080574 C20orf70 Chromosome 20 open reading frame 70 ENST00000378239 NM_015701 C2orf30 Chromosome 2 open reading frame 30 ENST00000245907 NM_000064 C3 Complement component 3 ENST00000383793 C3orf20 Chromosome 3 open reading frame 20 ENST00000383805 NM_173472 C3orf24 Chromosome 3 open reading frame 24 ENST00000344697 NM_032806 C3orf39 Chromosome 3 open reading frame 39 ENST00000367070 NM_000715 C4BPA Complement component 4 binding protein, alpha ENST00000367659 NM_021243.2 C6orf115 Chromosome 6 open reading frame 115 ENST00000275228 NM_052831 C6orf192 Chromosome 6 open reading frame 192 ENST00000331399 NM_152738 C6orf218 Chromosome 6 open reading frame 218 ENST00000368475 NM_001100411.1 C6orf60 Chromosome 6 open reading NM_024581.4 frame 60 ENST00000368596 C6orf78 ENST00000289989 NM_001013842 C8orf58 Chromosome 8 open reading frame 58 ENST00000378956 NM_148178 C9orf23 Chromosome 9 open reading NM_148179 frame 23 ENST00000338437 NM_001014435.1 CA7 Carbonic anhydrase VII NM_005182 ENST00000378357 NM_001216 CA9 Carbonic anhydrase IX ENST00000316803 NM_001033677 CABP1 Calcium binding protein 1 NM_004276 NM_031205 ENST00000360228 NM_000068.3 CACNA1A Calcium channel, voltage- NM_023035.2 dependent, P/Q type, alpha 1A subunit ENST00000288197 NM_018398.2 CACNA2D3 Calcium channel, voltage- dependent, alpha 2/delta 3 subunit ENST00000252729 NM_031897 CACNG6 Calcium channel, voltage- NM_145814 dependent, gamma subunit 6 NM_145815 ENST00000296742 CAGE1 Cancer antigen 1 ENST00000339300 NM_138793 CANT1 Calcium activated nucleotidase 1 ENST00000270361 CAPN10 Calpain 10 ENST00000354537 NM_006615 CAPN9 Calpain 9 NM_016452 ENST00000380525 NM_001014437.1 CARS Cysteinyl-tRNA synthetase NM_001014438.1 NM_001751 NM_139273.2 ENST00000264645 CASC3 Cancer susceptibility candidate 3 ENST00000356473 NM_001080124.1 CASP8 Caspase 8, apoptosis-related NM_001080125.1 cysteine peptidase NM_001228.4 NM_033355 NM_033356 NM_033358 ENST00000382436 CBWD1 COBW domain containing 1 ENST00000377349 CBWD3 ENST00000303601 NM_145020 CCDC11 Coiled-coil domain containing 11 ENST00000370276 NM_206886.2 CCDC18 Coiled-coil domain containing 18 ENST00000373602 CCDC28B Coiled-coil domain containing 28B ENST00000284400 NM_001037325 CCDC46 Coiled-coil domain containing 46 NM_145036 ENST00000321895 CCDC71 Coiled-coil domain containing 71 ENST00000377638 CCDC88 ENST00000219244 NM_002987 CCL17 Chemokine (C-C motif) ligand 17 ENST00000368261 NM_001008800 CCT3 Chaperonin containing TCP1, NM_001008883.1 subunit 3 (gamma) NM_005998 ENST00000322008 CD151 CD151 molecule (Raph blood group) ENST00000367063 NM_000574 CD55 CD55 molecule, decay accelerating factor for complement (Cromer blood group) ENST00000381845 NM_017913 CDC37L1 Cell division cycle 37 homolog (S. cerevisiae)-like 1 ENST00000361246 NM_006035 CDC42BPB CDC42 binding protein kinase beta (DMPK-like) ENST00000341529 NM_001795 CDH5 Cadherin 5, type 2, VE-cadherin (vascular epithelium) ENST00000268383 NM_001802 CDR2 Cerebellar degeneration-related protein 2, 62 kDa ENST00000382279 CDY1_HUMAN ENST00000306882 NM_004680 CDY1B Chromodomain protein, Y- NM_170723 linked, 1B NM_001003894 NM_001003895 ENST00000372927 CENPI Centromere protein I ENST00000381884 NM_018451 CENPJ Centromere protein J ENST00000262127 CEP76 Centrosomal protein 76 kDa ENST00000355558 CFLAR CASP8 and FADD-like apoptosis regulator ENST00000372833 CHCH1_HUMAN ENST00000290913 CHCHD6 Coiled-coil-helix-coiled-coil-helix domain containing 6 ENST00000342610 CHRD Chordin ENST00000289957 NM_000749 CHRNB3 Cholinergic receptor, nicotinic, beta 3 ENST00000308064 NM_003654 CHST1 Carbohydrate (keratan sulfate Gal-6) sulfotransferase 1 ENST00000358237 CI068_HUMAN ENST00000287159 CI070_HUMAN ENST00000269878 NM_054113 CIB3 Calcium and integrin binding family member 3 ENST00000323319 CLDN22 ENST00000355690 NM_138337 CLEC12A C-type lectin domain family 12, NM_201623 member A NM_205852 ENST00000261340 NM_001004419 CLEC2D C-type lectin domain family 2, NM_013269 member D ENST00000316308 CLK4 CDC-like kinase 4 ENST00000245816 CLPP ClpP caseinolytic peptidase, ATP-dependent, proteolytic subunit homolog (E. coli) ENST00000281129 CN145_HUMAN ENST00000272602 NM_001079878.1 CNGA3 Cyclic nucleotide gated channel NM_001298 alpha 3 ENST00000356162 NM_001008225.1 CNOT4 CCR4-NOT transcription NM_013316.2 complex, subunit 4 ENST00000307431 NM_033401.3 CNTNAP4 Contactin associated protein-like 4 NM_138994 ENST00000307149 COG7 Component of oligomeric golgi complex 7 ENST00000373668 NM_001856.3 COL16A1 Collagen, type XVI, alpha 1 ENST00000370819 NM_030820.3 COL21A1 Collagen, type XXI, alpha 1 ENST00000328333 NM_000094 COL7A1 Collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, dominant and recessive) ENST00000261037 COL8A1 Collagen, type VIII, alpha 1 ENST00000333188 COPB2 Coatomer protein complex, subunit beta 2 (beta prime) ENST00000253484 NM_001866 COX7B Cytochrome c oxidase subunit VIIb ENST00000314133 NM_004074 COX8A Cytochrome c oxidase subunit 8A (ubiquitous) ENST00000264193 NM_000097 CPOX Coproporphyrinogen oxidase ENST00000378951 CPSF3L Cleavage and polyadenylation specific factor 3-like ENST00000294997 CR1L Complement component (3b/4b) receptor 1-like ENST00000367401 NM_201253 CRB1 Crumbs homolog 1 (Drosophila) ENST00000339139 CRISP2 Cysteine-rich secretory protein 2 ENST00000262982 NM_001316 CSE1L CSE1 chromosome segregation 1-like (yeast) ENST00000331769 NM_000759 CSF3 Colony stimulating factor 3 NM_172219.1 (granulocyte) NM_172220 ENST00000383738 NM_006574 CSPG5 Chondroitin sulfate proteoglycan 5 (neuroglycan C) ENST00000311083 CSRP2 Cysteine and glycine-rich protein 2 ENST00000201961 CT112_HUMAN ENST00000361944 NM_014633 CTR9 Ctr9, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) ENST00000368980 NM_000396 CTSK Cathepsin K ENST00000217131 NM_001336 CTSZ Cathepsin Z ENST00000310126 CU058_HUMAN ENST00000372453 NM_173494 CXorf41 Chromosome X open reading frame 41 ENST00000285949 CYP26C1 Cytochrome P450, family 26, subfamily C, polypeptide 1 ENST00000371364 NM_016593 CYP39A1 Cytochrome P450, family 39, subfamily A, polypeptide 1 ENST00000336411 NM_017460 CYP3A4 Cytochrome P450, family 3, subfamily A, polypeptide 4 ENST00000379654 NM_022820 CYP3A43 Cytochrome P450, family 3, NM_057095 subfamily A, polypeptide 43 NM_057096 ENST00000368336 NM_004632 DAP3 Death associated protein 3 NM_033657 ENST00000250863 NM_001351.2 DAZL Deleted in azoospermia-like ENST00000355857 DBI Diazepam binding inhibitor (GABA receptor modulator, acyl- Coenzyme A binding protein) ENST00000339452 NM_017639 DCHS2 Dachsous 2 (Drosophila) ENST00000378278 NM_001033855 DCLRE1C DNA cross-link repair 1C (PSO2 NM_001033857 homolog, S. cerevisiae) NM_001033858 NM_022487 ENST00000368419 NM_152494 DCST1 DC-STAMP domain containing 1 ENST00000378601 DDB2 Damage-specific DNA binding protein 2, 48 kDa ENST00000378233 DDX3X_HUMAN ENST00000258772 DDX56 DEAD (Asp-Glu-Ala-Asp) box polypeptide 56 ENST00000381131 NM_018369 DEPDC1B DEP domain containing 1B ENST00000025429 NM_015954.2 DERA 2-deoxyribose-5-phosphate aldolase homolog (C. elegans) ENST00000374057 NM_001083885.1 DFNB31 Deafness, autosomal recessive NM_015404 31 ENST00000284688 NM_018180 DHX32 DEAH (Asp-Glu-Ala-His) box polypeptide 32 ENST00000266070 NM_022105 DIDO1 Death inducer-obliterator 1 NM_033081 NM_080796 NM_080797 ENST00000366636 DISC1 Disrupted in schizophrenia 1 ENST00000373347 DLGP3_HUMAN ENST00000222598 DLX5 Distal-less homeobox 5 ENST00000379075 NM_001035516.1 DMKN Dermokine NM_033317 ENST00000373718 NM_021800 DNAJC12 DnaJ (Hsp40) homolog, NM_201262 subfamily C, member 12 ENST00000382564 NM_145261 DNAJC19 DnaJ (Hsp40) homolog, subfamily C, member 19 ENST00000276570 DNAJC5B DnaJ (Hsp40) homolog, subfamily C, member 5 beta ENST00000367732 NM_015569.2 DNM3 Dynamin 3 ENST00000268793 NM_022357 DPEP3 Dipeptidase 3 ENST00000263084 DPH1 DPH1 homolog (S. cerevisiae) ENST00000370107 DPH5_HUMAN ENST00000242158 DRC1A_HUMAN ENST00000305784 DTYMK Deoxythymidylate kinase (thymidylate kinase) ENST00000358896 NM_017803 DUS2L Dihydrouridine synthase 2-like, SMM1 homolog (S. cerevisiae) ENST00000380838 NM_004422 DVL2 Dishevelled, dsh homolog 2 (Drosophila) ENST00000260605 NM_001012665.1 DYNC2LI1 Dynein, cytoplasmic 2, light NM_016008 intermediate chain 1 ENST00000367089 NM_006519 DYNLT1 Dynein, light chain, Tctex-type 1 ENST00000250024 NM_024680 E2F8 E2F transcription factor 8 ENST00000221847 EBI3 Epstein-Barr virus induced gene 3 ENST00000378284 NM_032565 EBPL Emopamil binding protein-like ENST00000264205 NM_001397 ECE1 Endothelin converting enzyme 1 ENST00000351385 NM_001037324 ECE2 Endothelin converting enzyme 2 NM_001100120.1 NM_001100121.1 NM_014693 NM_032331 ENST00000304546 ECEL1 Endothelin converting enzyme- like 1 ENST00000220959 EDD1 ENST00000264263 EFG1_HUMAN ENST00000333845 NM_005155 EGFL8 EGF-like-domain, multiple 8 NM_030652 NM_138717 ENST00000253108 EIF3S4 ENST00000381683 EIF3S6IP ENST00000228741 NM_005230 ELK3 ELK3, ETS-domain protein (SRF accessory protein 2) ENST00000319359 ELL3 Elongation factor RNA polymerase II-like 3 ENST00000163344 NM_022821 ELOVL1 Elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 1 ENST00000334192 NM_001008707 EML1 Echinoderm microtubule NM_004434 associated protein like 1 ENST00000372642 ENDOG Endonuclease G ENST00000376666 ENTPD6 Ectonucleoside triphosphate diphosphohydrolase 6 (putative function) ENST00000374311 ERGIC3 ERGIC and golgi 3 ENST00000355449 EVL Enah/Vasp-like ENST00000370902 NM_016046 EXOSC1 Exosome component 1 ENST00000320356 EZH2 Enhancer of zeste homolog 2 (Drosophila) ENST00000375551 NM_000504 F10 Coagulation factor X ENST00000355910 NM_001007524 F8A3 Coagulation factor VIII- associated (intronic transcript) 3 ENST00000301838 NM_003824 FADD Fas (TNFRSF6)-associated via death domain ENST00000338446 NM_001033030 FAIM Fas apoptotic inhibitory molecule NM_001033031 NM_001033032 NM_018147 ENST00000216214 NM_017911 FAM118A Family with sequence similarity 118, member A ENST00000336378 FAM21D ENST00000359512 FAM39A ENST00000357985 FAM3B Family with sequence similarity 3, member B ENST00000298575 NM_152421 FAM69B Family with sequence similarity 69, member B ENST00000373736 FAM77C ENST00000357809 FAM82A Family with sequence similarity 82, member A ENST00000300030 FAM96A Family with sequence similarity 96, member A ENST00000314606 FARSLA ENST00000367721 NM_000639 FASLG Fas ligand (TNF superfamily, member 6) ENST00000369956 FBX37_HUMAN ENST00000258200 FBXL8 ENST00000382824 NM_012173 FBXO25 F-box protein 25 NM_183420 NM_183421 ENST00000368176 FCRL1 Fc receptor-like 1 ENST00000368181 NM_030764 FCRL2 Fc receptor-like 2 NM_138738 ENST00000339348 NM_001004310 FCRL6 Fc receptor-like 6 ENST00000371489 NM_013451.2 FER1L3 Fer-1-like 3, myoferlin (C. elegans) NM_133337.1 ENST00000343958 FGD6_HUMAN ENST00000370603 NM_004114 FGF13 Fibroblast growth factor 13 NM_033642 ENST00000341420 NM_013281 FLRT3 Fibronectin leucine rich NM_198391 transmembrane protein 3 ENST00000357867 NM_002026 FN1 Fibronectin 1 NM_054034.2 NM_212474 NM_212476.1 NM_212482.1 ENST00000379745 NM_022823 FNDC4 Fibronectin type III domain containing 4 ENST00000370019 NM_173532 FNDC7 Fibronectin type III domain containing 7 ENST00000302177 NM_004497 FOXA3 Forkhead box A3 ENST00000354663 NM_005479 FRAT1 Frequently rearranged in advanced T-cell lymphomas ENST00000373018 NM_006653 FRS3 Fibroblast growth factor receptor substrate 3 ENST00000166139 NM_005860 FSTL3 Follistatin-like 3 (secreted glycoprotein) ENST00000250113 NM_004860.2 FXR2 Fragile X mental retardation, autosomal homolog 2 ENST00000342879 FXYD5 FXYD domain containing ion transport regulator 5 ENST00000367029 G0S2 G0/G1switch 2 ENST00000269097 G6PC3 Glucose 6 phosphatase, catalytic, 3 ENST00000259056 GALNT5 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 5 (GalNAc-T5) ENST00000227756 GALNTL4 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase- like 4 ENST00000373387 GARNL3 GTPase activating Rap/RanGAP domain-like 3 ENST00000265296 NM_002047.2 GARS Glycyl-tRNA synthetase ENST00000357389 GAS6 Growth arrest-specific 6 ENST00000341105 GATA2 GATA binding protein 2 ENST00000372043 GBGT1 Globoside alpha-1,3-N- acetylgalactosaminyltransferase 1 ENST00000233612 NM_012198 GCA Grancalcin, EF-hand calcium binding protein ENST00000379596 NM_001491 GCNT2 Glucosaminyl (N-acetyl) NM_145649 transferase 2, I-branching NM_145655 enzyme (I blood group) ENST00000322348 NM_016591 GCNT4 Glucosaminyl (N-acetyl) transferase 4, core 2 (beta-1,6- N- acetylglucosaminyltransferase) ENST00000378673 NM_005260 GDF9 Growth differentiation factor 9 ENST00000253778 NM_005110.2 GFPT2 Glutamine-fructose-6-phosphate transaminase 2 ENST00000313543 GIMAP7 GTPase, IMAP family member 7 ENST00000357424 NM_004123 GIP Gastric inhibitory polypeptide ENST00000241125 NM_021954 GJA3 Gap junction protein, alpha 3, 46 kDa ENST00000331334 GLRX5 Glutaredoxin 5 ENST00000318348 NM_016433 GLTP Glycolipid transfer protein ENST00000303210 GNB2 Guanine nucleotide binding protein (G protein), beta polypeptide 2 ENST00000354540 NM_014366 GNL3 Guanine nucleotide binding NM_206825.1 protein-like 3 (nucleolar) NM_206826.1 ENST00000225567 NM_004287.3 GOSR2 Golgi SNAP receptor complex NM_054022 member 2 ENST00000334304 NM_145290 GPR125 G protein-coupled receptor 125 ENST00000267015 NM_020370 GPR84 G protein-coupled receptor 84 ENST00000315614 GPS2 G protein pathway suppressor 2 ENST00000309731 NM_001012642 GRAMD2 GRAM domain containing 2 ENST00000347612 GRIN2C Glutamate receptor, ionotropic, N-methyl D-aspartate 2C ENST00000369106 GRK5 G protein-coupled receptor kinase 5 ENST00000296479 GRM2 Glutamate receptor, metabotropic 2 ENST00000319065 NM_000843 GRM6 Glutamate receptor, metabotropic 6 ENST00000256857 NM_001012512.1 GRP Gastrin-releasing peptide NM_001012513.1 NM_002091 ENST00000086933 GSCL ENST00000219627 NM_002094.2 GSPT1 G1 to S phase transition 1 ENST00000340438 NM_018094 GSPT2 G1 to S phase transition 2 ENST00000221130 NM_000637 GSR Glutathione reductase ENST00000267869 NM_004492 GTF2A2 General transcription factor IIA, 2, 12 kDa ENST00000376329 GTF2H4 General transcription factor IIH, polypeptide 4, 52 kDa ENST00000332377 NM_207118 GTF2H5 General transcription factor IIH, polypeptide 5 ENST00000372108 NM_012087 GTF3C5 General transcription factor IIIC, polypeptide 5, 63 kDa ENST00000323798 NM_002103 GYS1 Glycogen synthase 1 (muscle) ENST00000296417 H2AFZ H2A histone family, member Z ENST00000375852 NM_002110 HCK Hemopoietic cell kinase ENST00000314583 HCLS1 Hematopoietic cell-specific Lyn substrate 1 ENST00000373705 HCRTR1 Hypocretin (orexin) receptor 1 ENST00000262069 NM_014707.1 HDAC9 Histone deacetylase 9 NM_058176.2 NM_058177.2 NM_178423.1 NM_178425.2 ENST00000300605 HDHD2 Haloacid dehalogenase-like hydrolase domain containing 2 ENST00000374178 NM_031219 HDHD3 Haloacid dehalogenase-like hydrolase domain containing 3 ENST00000303775 HEMK2_HUMAN ENST00000329138 HGS Hepatocyte growth factor- regulated tyrosine kinase substrate ENST00000370940 NM_001031693 HHLA3 HERV-H LTR-associating 3 NM_001036645 NM_001036646 NM_007071 ENST00000229633 NM_138571 HINT3 Histidine triad nucleotide binding protein 3 ENST00000336926 NM_005338 HIP1 Huntingtin interacting protein 1 ENST00000360010 HKR1 GLI-Kruppel family member HKR1 ENST00000366903 HLX1 ENST00000380749 HMGN1 High-mobility group nucleosome binding domain 1 ENST00000376263 NM_002140 HNRPK Heterogeneous nuclear NM_031262 ribonucleoprotein K NM_031263 ENST00000336726 NM_152510.2 HORMAD2 HORMA domain containing 2 ENST00000222753 NM_000522 HOXA13 Homeobox A13 ENST00000239144 NM_024016 HOXB8 Homeobox B8 ENST00000243108 HOXC6 ENST00000306324 NM_014621 HOXD4 Homeobox D4 ENST00000299671 HSBP1 Heat shock factor binding protein 1 ENST00000225929 NM_000413 HSD17B1 Hydroxysteroid (17-beta) dehydrogenase 1 ENST00000373024 I5P2_HUMAN ENST00000235971 ID3 Inhibitor of DNA binding 3, dominant negative helix-loop- helix protein ENST00000370747 IFI44 Interferon-induced protein 44 ENST00000276927 NM_024013 IFNA1 Interferon, alpha 1 ENST00000380205 NM_002170 IFNA8 Interferon, alpha 8 ENST00000229135 NM_000619 IFNG Interferon, gamma ENST00000296266 NM_018262 IFT122 Intraflagellar transport 122 NM_052985 homolog (Chlamydomonas) NM_052989 NM_052990 ENST00000198587 IGSF9 Immunoglobulin superfamily, member 9 ENST00000367120 NM_014002 IKBKE Inhibitor of kappa light polypeptide gene enhancer in B- cells, kinase epsilon ENST00000290200 IL10RB Interleukin 10 receptor, beta ENST00000305579 IL12A Interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) ENST00000322153 NM_005535.1 IL12RB1 Interleukin 12 receptor, beta 1 NM_153701 ENST00000264260 NM_003853 IL18RAP Interleukin 18 receptor accessory protein ENST00000367095 NM_005449 IL24 Interleukin 24 ENST00000276110 IL2RG Interleukin 2 receptor, gamma (severe combined immunodeficiency) ENST00000368485 NM_000565 IL6R Interleukin 6 receptor NM_181359 ENST00000259239 IMP4 IMP4, U3 small nucleolar ribonucleoprotein, homolog (yeast) ENST00000269159 IMPA2 Inositol(myo)-1(or 4)- monophosphatase 2 ENST00000322522 NM_002194 INPP1 Inositol polyphosphate-1- phosphatase ENST00000265239 IQCG IQ motif containing G ENST00000356669 NM_016123 IRAK4 Interleukin-1 receptor-associated kinase 4 ENST00000258886 NM_004136 IREB2 Iron-responsive element binding protein 2 ENST00000303389 IRF2 Interferon regulatory factor 2 ENST00000268638 NM_002163 IRF8 Interferon regulatory factor 8 ENST00000379231 ISG20L1 Interferon stimulated exonuclease gene 20 kDa-like 1 ENST00000249842 NM_005545 ISLR Immunoglobulin superfamily NM_201526 containing leucine-rich repeat ENST00000268297 NM_005353 ITGAD Integrin, alpha D ENST00000335404 NM_198510 ITIH5L Inter-alpha (globulin) inhibitor H5-like ENST00000380883 NM_006277 ITSN2 Intersectin 2 NM_019595 NM_147152.1 ENST00000383816 JAGN1 Jagunal homolog 1 (Drosophila) ENST00000327520 JHD2C_HUMAN ENST00000335080 NM_018039 JMJD2D Jumonji domain containing 2D ENST00000335647 NM_007044 KATNA1 Katanin p60 (ATPase- containing) subunit A 1 ENST00000328224 NM_002233.2 KCNA4 Potassium voltage-gated channel, shaker-related subfamily, member 4 ENST00000316071 NM_002241 KCNJ10 Potassium inwardly-rectifying channel, subfamily J, member 10 ENST00000233826 NM_002242 KCNJ13 Potassium inwardly-rectifying channel, subfamily J, member 13 ENST00000295101 NM_002239 KCNJ3 Potassium inwardly-rectifying channel, subfamily J, member 3 ENST00000366621 KCNK1 Potassium channel, subfamily K, member 1 ENST00000353172 KCTD14 ENST00000379108 NM_198404 KCTD4 Potassium channel tetramerisation domain containing 4 ENST00000360029 NM_198353 KCTD8 Potassium channel tetramerisation domain containing 8 ENST00000297423 NM_001080394.1 KIAA0146 KIAA0146 ENST00000370992 KIAA0690 ENST00000287546 KIAA0804 ENST00000283351 NM_014939 KIAA1012 KIAA1012 ENST00000264501 NM_015312.2 KIAA1109 KIAA1109 ENST00000296121 KIAA1143 KIAA1143 ENST00000328839 NM_020958 KIAA1622 KIAA1622 NM_058237 ENST00000369271 KIAA1914 ENST00000378843 NM_022113.3 KIF13A Kinesin family member 13A ENST00000353409 NM_015074 KIF1B Kinesin family member 1B NM_183416 ENST00000378746 NM_007054 KIF3A Kinesin family member 3A ENST00000332780 NM_173546 KLHDC8B Kelch domain containing 8B ENST00000378222 NM_002267 KPNA3 Karyopherin alpha 3 (importin alpha 4) ENST00000329122 NM_181602 KRTAP6-1 Keratin associated protein 6-1 ENST00000251646 KRTHA3B ENST00000293670 KRTHB3 ENST00000264170 NM_001032998 KYNU Kynureninase (L-kynurenine NM_003937 hydrolase) ENST00000373134 L3MBTL ENST00000381167 LAPTM4A Lysosomal-associated protein transmembrane 4 alpha ENST00000357788 LCN8 Lipocalin 8 ENST00000371103 LCOR_HUMAN ENST00000280706 NM_144972 LDHAL6A Lactate dehydrogenase A-like 6A ENST00000254301 LGALS3 Lectin, galactoside-binding, soluble, 3 ENST00000263726 NM_033343 LHX4 LIM homeobox 4 ENST00000261203 LIN7A Lin-7 homolog A (C. elegans) ENST00000267102 LMBR1L Limb region 1 homolog (mouse)- like ENST00000296603 NM_001007527 LMBRD2 LMBR1 domain containing 2 ENST00000368300 NM_005572 LMNA Lamin A/C NM_170707 NM_170708 ENST00000376633 NM_002335 LRP5 Low density lipoprotein receptor- related protein 5 ENST00000261349 NM_002336 LRP6 Low density lipoprotein receptor- related protein 6 ENST00000373324 NM_001005373 LRSAM1 Leucine rich repeat and sterile NM_001005374 alpha motif containing 1 NM_138361 ENST00000379953 LY86 Lymphocyte antigen 86 ENST00000244333 LYPD3 LY6/PLAUR domain containing 3 ENST00000374505 NM_007260 LYPLA2 Lysophospholipase II NR_001444.3 ENST00000215739 NM_006767 LZTR1 Leucine-zipper-like transcription regulator 1 ENST00000372173 NM_001003690.1 MAD2L1BP MAD2L1 binding protein NM_014628 ENST00000285879 NM_005462 MAGEC1 Melanoma antigen family C, 1 ENST00000261483 MAN2A1 Mannosidase, alpha, class 2A, member 1 ENST00000366920 NM_005922 MAP3K4 Mitogen-activated protein kinase NM_006724 kinase kinase 4 ENST00000357955 NM_004635 MAPKAPK3 Mitogen-activated protein kinase-activated protein kinase 3 ENST00000294506 MATN1 Matrilin 1, cartilage matrix protein ENST00000359787 MB Myoglobin ENST00000271648 NM_021960 MCL1 Myeloid cell leukemia sequence NM_182763 1 (BCL2-related) ENST00000230321 NM_005586 MDFI MyoD family inhibitor ENST00000267984 NM_022566 MESDC1 Mesoderm development candidate 1 ENST00000372811 MFSD2 Major facilitator superfamily domain containing 2 ENST00000312952 NM_004668.1 MGAM Maltase-glucoamylase (alpha- glucosidase) ENST00000371994 NM_004897 MINPP1 Multiple inositol polyphosphate histidine phosphatase, 1 ENST00000231790 NM_000249 MLH1 MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) ENST00000338530 NM_001042467.1 MLPH Melanophilin NM_024101 ENST00000182377 NM_018099 MLSTD1 Male sterility domain containing 1 ENST00000345114 NM_032951 MLXIPL MLX interacting protein-like NM_032952.2 NM_032953.2 NM_032954 ENST00000262065 NM_012329 MMD Monocyte to macrophage differentiation-associated ENST00000368141 NM_002432 MNDA Myeloid cell nuclear differentiation antigen ENST00000296473 MON1A MON1 homolog A (yeast) ENST00000333676 MRPL12 Mitochondrial ribosomal protein L12 ENST00000306185 MRPL13 Mitochondrial ribosomal protein L13 ENST00000379666 MRPL33 Mitochondrial ribosomal protein L33 ENST00000309352 NM_032478 MRPL38 Mitochondrial ribosomal protein L38 ENST00000370234 NM_032112 MRPL43 Mitochondrial ribosomal protein NM_176792 L43 NM_176793 NM_176794 ENST00000312513 NM_032351 MRPL45 Mitochondrial ribosomal protein L45 ENST00000372940 NM_016065 MRPS16 Mitochondrial ribosomal protein S16 ENST00000313608 MRPS23 Mitochondrial ribosomal protein S23 ENST00000276585 MRPS28 Mitochondrial ribosomal protein S28 ENST00000322684 MSI2 Musashi homolog 2 (Drosophila) ENST00000314404 NM_017762.2 MTMR10 Myotubularin related protein 10 ENST00000323456 NM_004687 MTMR4 Myotubularin related protein 4 ENST00000374852 NM_017677 MTMR8 Myotubularin related protein 8 ENST00000381954 MUC20 Mucin 20, cell surface associated ENST00000303270 MXD3 MAX dimerization protein 3 ENST00000252102 NDUFA2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8 kDa ENST00000381417 NDUFS4 NADH dehydrogenase (ubiquinone) Fe—S protein 4, 18 kDa (NADH-coenzyme Q reductase) ENST00000375569 NECAP2 NECAP endocytosis associated 2 ENST00000250495 NEDD8 Neural precursor cell expressed, developmentally down-regulated 8 ENST00000379072 NM_012224.1 NEK1 NIMA (never in mitosis gene a)- related kinase 1 ENST00000366999 NM_002497 NEK2 NIMA (never in mitosis gene a)- related kinase 2 ENST00000356175 NM_000267 NF1 Neurofibromin 1 NM_001042492.1 (neurofibromatosis, von Recklinghausen disease, Watson disease) ENST00000355469 NM_145912 NFAM1 NFAT activating protein with ITAM motif 1 ENST00000361004 NM_006164.2 NFE2L2 Nuclear factor (erythroid-derived 2)-like 2 ENST00000375724 NM_005384 NFIL3 Nuclear factor, interleukin 3 regulated ENST00000368009 NM_005600 NIT1 Nitrilase 1 ENST00000285279 NM_030796.3 ENST00000360476 NM_021077 NMB Neuromedin B NM_205858.1 ENST00000255262 NM_020167 NMUR2 Neuromedin U receptor 2 ENST00000382421 NOL1 Nucleolar protein 1, 120 kDa ENST00000328848 NM_018648 NOLA3 Nucleolar protein family A, member 3 (H/ACA small nucleolar RNPs) ENST00000375043 NM_004557 NOTCH4 Notch homolog 4 (Drosophila) ENST00000367158 NM_015718 NOX3 NADPH oxidase 3 ENST00000301284 NP_001001520.1 ENST00000389349 NP_001001671.1 ENST00000304823 NP_001004341.1 ENST00000351071 NP_001005751.1 ENST00000333305 NP_001007190.1 ENST00000370732 NP_001007552.1 ENST00000341942 NP_001008396.1 ENST00000298943 NP_001010908.1 ENST00000378704 NP_001012457.1 ENST00000370494 NP_001013007.1 ENST00000344380 NP_001013646.1 ENST00000378909 NP_001017363.1 ENST00000370743 NP_001017417.1 ENST00000370737 NP_001017435.1 ENST00000381461 NP_001017969.1 ENST00000295220 NP_001025167.1 ENST00000374412 NP_001034934.1 ENST00000294916 NP_001035043.2 ENST00000382142 NP_001035536.1 ENST00000329687 NP_001111.2 ENST00000355848 NP_006324.1 ENST00000323199 NP_031375.3 ENST00000357765 NP_054763.2 ENST00000357899 NP_054874.3 ENST00000377264 NP_055919.1 ENST00000381237 NP_056174.1 ENST00000296444 NP_057563.3 ENST00000313565 NP_060000.1 ENST00000321489 NP_060028.2 ENST00000367501 NP_060143.3 ENST00000265154 NP_060170.1 ENST00000238788 NP_060197.3 ENST00000357242 NP_060222.2 ENST00000379207 NP_060463.1 ENST00000358591 NP_060741.2 ENST00000358867 NP_060950.2 ENST00000329540 NP_061930.1 ENST00000359236 NP_061959.2 ENST00000270066 NP_061981.1 ENST00000263657 NP_064528.1 ENST00000336353 NP_064580.1 ENST00000319688 NP_065789.1 ENST00000368842 NP_071409.2 ENST00000317623 NP_071940.3 ENST00000295079 NP_078796.1 ENST00000371410 NP_078804.1 ENST00000358067 NP_078896.3 ENST00000238936 NP_079065.2 ENST00000278886 NP_079452.3 ENST00000272521 NP_085054.1 ENST00000369218 NP_110423.3 ENST00000263776 NP_115981.1 ENST00000367003 NP_116094.2 ENST00000376396 NP_296375.1 ENST00000300079 NP_542392.2 ENST00000290894 NP_612365.1 ENST00000341392 NP_620134.2 ENST00000355682 NP_653178.1 ENST00000301037 NP_653211.1 ENST00000002125 NP_653337.1 ENST00000335360 NP_689552.2 ENST00000281961 NP_689603.1 ENST00000282259 NP_689618.2 ENST00000367136 NP_689704.3 ENST00000370720 NP_689795.2 ENST00000296468 NP_689991.1 ENST00000292616 NP_690852.1 ENST00000304584 NP_699196.1 ENST00000296953 NP_705835.1 ENST00000265453 NP_775795.2 ENST00000329378 NP_775936.1 ENST00000378660 NP_775966.1 ENST00000335211 NP_840059.1 ENST00000380814 NP_861450.1 ENST00000334588 NP_872620.1 ENST00000285718 NP_878908.1 ENST00000383694 NP_878913.1 ENST00000340369 NP_919269.2 ENST00000343063 NP_919288.1 ENST00000275053 NP_940870.1 ENST00000306862 NP_940968.1 ENST00000237186 NP_944602.1 ENST00000317449 NP_981967.1 ENST00000354805 NP_982273.1 ENST00000377137 NP_997211.1 ENST00000357485 NP_997646.1 ENST00000339255 NM_020448 NPAL3 NIPA-like domain containing 3 ENST00000269228 NM_000271 NPC1 Niemann-Pick disease, type C1 ENST00000265634 NM_002523 NPTX2 Neuronal pentraxin II ENST00000242152 NPY Neuropeptide Y ENST00000358384 NR_002822.1 ENST00000332894 NR2F2 Nuclear receptor subfamily 2, group F, member 2 ENST00000291442 NM_005234 NR2F6 Nuclear receptor subfamily 2, group F, member 6 ENST00000314171 NM_030759 NRBF2 Nuclear receptor binding factor 2 ENST00000382740 NSG1_HUMAN ENST00000219066 NTHL1 Nth endonuclease III-like 1 (E. coli) ENST00000231498 NU155_HUMAN ENST00000361681 NU6M_HUMAN ENST00000367157 NUAK2 NUAK family, SNF1-like kinase, 2 ENST00000262302 NUBP2 Nucleotide binding protein 2 (MinD homolog, E. coli) ENST00000334513 NUD17_HUMAN ENST00000339154 NUDT6 Nudix (nucleoside diphosphate linked moiety X)-type motif 6 ENST00000366680 NM_018230 NUP133 Nucleoporin 133 kDa ENST00000294172 NXF1 Nuclear RNA export factor 1 ENST00000372107 NM_018698 NXT2 Nuclear transport factor 2-like export factor 2 ENST00000324607 OACT1 ENST00000366706 OBSCN Obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF ENST00000334011 NM_152635 OIT3 Oncoprotein induced transcript 3 ENST00000371797 NM_006334 OLFM1 Olfactomedin 1 NM_014279 ENST00000333973 NM_001004738 OR5L1 Olfactory receptor, family 5, subfamily L, member 1 ENST00000297431 NM_002553 ORC5L Origin recognition complex, NM_181747.1 subunit 5-like (yeast) ENST00000313733 NM_014835 OSBPL2 Oxysterol binding protein-like 2 NM_144498 ENST00000263650 NM_020896 OSBPL5 Oxysterol binding protein-like 5 NM_145638 ENST00000378500 NM_000531 OTC Ornithine carbamoyltransferase ENST00000339475 NM_021728 OTX2 Orthodenticle homeobox 2 NM_172337.1 ENST00000378434 NM_005767 P2RY5 Purinergic receptor P2Y, G- protein coupled, 5 ENST00000360935 P54762-4 ENST00000318607 NM_002568 PABPC1 Poly(A) binding protein, cytoplasmic 1 ENST00000381859 NM_030979 PABPC3 Poly(A) binding protein, cytoplasmic 3 ENST00000374284 NM_000437 PAFAH2 Platelet-activating factor acetylhydrolase 2, 40 kDa ENST00000265192 PAIP2 Poly(A) binding protein interacting protein 2 ENST00000378466 NM_018216 PANK4 Pantothenate kinase 4 ENST00000045065 NM_001003931.1 PARP3 Poly (ADP-ribose) polymerase NM_001003935.1 family, member 3 NM_005485.3 ENST00000368465 NM_020524 PBXIP1 Pre-B-cell leukemia homeobox interacting protein 1 ENST00000376286 PCCA Propionyl Coenzyme A carboxylase, alpha polypeptide ENST00000377922 NM_001040429 PCDH17 Protocadherin 17 ENST00000297529 NM_006197.3 PCM1 Pericentriolar material 1 ENST00000282096 PDE3B Phosphodiesterase 3B, cGMP- inhibited ENST00000227868 PDHX Pyruvate dehydrogenase complex, component X ENST00000219406 NM_006849.2 PDIA2 Protein disulfide isomerase family A, member 2 ENST00000005178 NM_002612 PDK4 Pyruvate dehydrogenase kinase, isozyme 4 ENST00000340532 NM_003687 PDLIM4 PDZ and LIM domain 4 ENST00000261313 PEBP1 Phosphatidylethanolamine binding protein 1 ENST00000367756 NM_000288 PEX7 Peroxisomal biogenesis factor 7 ENST00000296029 NM_002619 PF4 Platelet factor 4 (chemokine (C- X-C motif) ligand 4) ENST00000226524 NM_002620 PF4V1 Platelet factor 4 variant 1 ENST00000340802 PFKM Phosphofructokinase, muscle ENST00000321327 NM_024554 PGBD5 PiggyBac transposable element derived 5 ENST00000300408 PHB Prohibitin ENST00000361895 PHF15_HUMAN ENST00000327906 PHF7 PHD finger protein 7 ENST00000369409 NM_006623 PHGDH Phosphoglycerate dehydrogenase ENST00000328273 PHKG2 Phosphorylase kinase, gamma 2 (testis) ENST00000369604 PHTF1 Putative homeodomain transcription factor 1 ENST00000331075 NM_001002837.1 PIB5PA Phosphatidylinositol (4,5) NM_014422.2 bisphosphate 5-phosphatase, A ENST00000026218 PIGQ Phosphatidylinositol glycan anchor biosynthesis, class Q ENST00000291009 NM_002652 PIP Prolactin-induced protein ENST00000230643 NM_014386.2 PKD2L2 Polycystic kidney disease 2-like 2 ENST00000368452 PKIB Protein kinase (cAMP- dependent, catalytic) inhibitor beta ENST00000372764 NM_002658 PLAU Plasminogen activator, urokinase ENST00000325234 NM_000932 PLCB3 Phospholipase C, beta 3 (phosphatidylinositol-specific) ENST00000326631 PLEKHJ1 Pleckstrin homology domain containing, family J member 1 ENST00000381170 NM_006622 PLK2 Polo-like kinase 2 (Drosophila) ENST00000380965 PM14_HUMAN ENST00000368276 PMF1 Polyamine-modulated factor 1 ENST00000369216 PNLIPRP1 Pancreatic lipase-related protein 1 ENST00000254508 PO210_HUMAN ENST00000265465 NM_002689 POLA2 Polymerase (DNA directed), alpha 2 (70 kD subunit) ENST00000222572 PON2 Paraoxonase 2 ENST00000264231 POPDC2 Popeye domain containing 2 ENST00000229003 PP11_HUMAN ENST00000373232 PPA1 Pyrophosphatase (inorganic) 1 ENST00000269812 PPAP2C Phosphatidic acid phosphatase type 2C ENST00000309576 NM_005037 PPARG Peroxisome proliferator- NM_015869 activated receptor gamma NM_138711 NM_138712 ENST00000225174 NM_005729 PPIF Peptidylprolyl isomerase F (cyclophilin F) ENST00000367437 NM_139126 PPIL4 Peptidylprolyl isomerase (cyclophilin)-like 4 ENST00000295908 PPM1K Protein phosphatase 1K (PP2C domain containing) ENST00000328257 PPME1_HUMAN ENST00000376745 PPP1CA Protein phosphatase 1, catalytic subunit, alpha isoform ENST00000279387 PPP4C Protein phosphatase 4 (formerly X), catalytic subunit ENST00000229430 NM_002726 PREP Prolyl endopeptidase ENST00000296800 NM_006251 PRKAA1 Protein kinase, AMP-activated, NM_206907 alpha 1 catalytic subunit ENST00000378567 NM_001033581.1 PRKCZ Protein kinase C, zeta NM_001033582.1 NM_002744 ENST00000325748 PRKRA Protein kinase, interferon- inducible double stranded RNA dependent activator ENST00000361340 NM_001536.3 PRMT1 Protein arginine NM_198318.2 methyltransferase 1 NM_198319 ENST00000374477 PROCR Protein C receptor, endothelial (EPCR) ENST00000375547 NM_003891 PROZ Protein Z, vitamin K-dependent plasma glycoprotein ENST00000227524 NM_014502 PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae) ENST00000360614 PRSS15 ENST00000376376 NM_020200 PRTFDC1 Phosphoribosyl transferase domain containing 1 ENST00000291752 NM_002784 PSG9 Pregnancy specific beta-1- glycoprotein 9 ENST00000322215 PSMA1 Proteasome (prosome, macropain) subunit, alpha type, 1 ENST00000261303 PSMC1 Proteasome (prosome, macropain) 26S subunit, ATPase, 1 ENST00000219313 PSMD7 Proteasome (prosome, macropain) 26S subunit, non- ATPase, 7 ENST00000215071 NM_002812 PSMD8 Proteasome (prosome, macropain) 26S subunit, non- ATPase, 8 ENST00000338910 PSPC1 Paraspeckle component 1 ENST00000375275 PTCH ENST00000261266 PTPRB Protein tyrosine phosphatase, receptor type, B ENST00000354705 NM_002840 PTPRF Protein tyrosine phosphatase, NM_130440 receptor type, F ENST00000281171 NM_002848 PTPRO Protein tyrosine phosphatase, NM_030667 receptor type, O NM_030668.1 NM_030669.1 NM_030670.1 NM_030671.1 ENST00000335223 PTRH1 Peptidyl-tRNA hydrolase 1 homolog (S. cerevisiae) ENST00000329875 NM_006907 PYCR1 Pyrroline-5-carboxylate NM_153824 reductase 1 ENST00000382759 Q15379_HUMAN ENST00000300167 Q15885_HUMAN ENST00000389664 Q3B8N5_HUMAN ENST00000377441 Q4V339_HUMAN ENST00000284630 Q5H9U9_HUMAN ENST00000371125 Q5JQE8_HUMAN ENST00000358745 Q5JTY0_HUMAN ENST00000377380 Q5RIA9_HUMAN ENST00000355876 Q5SNT8_HUMAN ENST00000376284 Q5STD0_HUMAN ENST00000369586 Q5T5W8_HUMAN ENST00000377523 Q5T7N8_HUMAN ENST00000382086 Q5TI84_HUMAN ENST00000374801 Q5VW05_HUMAN ENST00000357846 Q6DRA6_HUMAN ENST00000357858 Q6IPT3_HUMAN ENST00000330280 Q6P1K8_HUMAN ENST00000376153 Q6P6C6_HUMAN ENST00000258884 Q6PCB6_HUMAN ENST00000293695 Q6PIF2_HUMAN ENST00000310694 Q6UTX4_HUMAN ENST00000371751 Q6ZP22_HUMAN ENST00000329807 Q6ZQP9_HUMAN ENST00000373364 Q6ZRV4_HUMAN ENST00000381934 Q6ZSM7_HUMAN ENST00000342355 Q6ZU04_HUMAN ENST00000377696 Q6ZUF0_HUMAN ENST00000375548 Q6ZUP0_HUMAN ENST00000370590 Q6ZUQ1_HUMAN ENST00000371863 Q6ZVB9_HUMAN ENST00000382314 Q86SG3-2 ENST00000334298 Q86TT0_HUMAN ENST00000307823 Q8N467_HUMAN ENST00000322053 Q8N675_HUMAN ENST00000356176 Q8N7L3_HUMAN ENST00000313294 Q8NA31_HUMAN ENST00000380816 Q8NA85_HUMAN ENST00000327685 Q8NBD7_HUMAN ENST00000277491 Q8NDA2_HUMAN ENST00000313807 Q8TAS2_HUMAN ENST00000358148 Q8TEB0_HUMAN ENST00000268314 Q96C12_HUMAN ENST00000339359 Q9BVY2_HUMAN ENST00000253461 Q9H693_HUMAN ENST00000261651 Q9H7M0_HUMAN ENST00000321536 Q9P188_HUMAN ENST00000267328 NM_017817 RAB20 RAB20, member RAS oncogene family ENST00000344445 NM_016277 RAB23 RAB23, member RAS oncogene NM_183227 family ENST00000375836 RAB3GAP1 RAB3 GTPase activating protein subunit 1 (catalytic) ENST00000373826 RAB42 RAB42, member RAS oncogene family ENST00000373538 NM_005833 RABEPK Rab9 effector protein with kelch motifs ENST00000337432 RAD51C RAD51 homolog C (S. cerevisiae) ENST00000368404 RAG1AP1 Recombination activating gene 1 activating protein 1 ENST00000372062 RALGDS Ral guanine nucleotide dissociation stimulator ENST00000374757 NM_002885 RAP1GAP RAP1 GTPase activating protein ENST00000319149 NM_000964 RARA Retinoic acid receptor, alpha NM_001024809.2 NM_001033603 ENST00000231572 NM_002887 RARS Arginyl-tRNA synthetase ENST00000220062 NM_016563 RASL12 RAS-like, family 12 ENST00000319715 NM_006910 RBBP6 Retinoblastoma binding protein 6 NM_018703 ENST00000369784 NM_022768 RBM15 RNA binding motif protein 15 ENST00000367006 RCOR3 REST corepressor 3 ENST00000367664 REPS1 RALBP1 associated Eps domain containing 1 ENST00000355710 NM_020630.4 RET Ret proto-oncogene NM_020975 ENST00000380071 RFC3 Replication factor C (activator 1) 3, 38 kDa ENST00000374596 RGL2 Ral guanine nucleotide dissociation stimulator-like 2 ENST00000367459 NM_002922 RGS1 Regulator of G-protein signaling 1 ENST00000206262 NM_012419 RGS17 Regulator of G-protein signaling 17 ENST00000343854 NM_004296 RGS6 Regulator of G-protein signaling 6 ENST00000268125 NM_000326 RLBP1 Retinaldehyde binding protein 1 ENST00000340900 RNASE1 Ribonuclease, RNase A family, 1 (pancreatic) ENST00000344624 RNASEN Ribonuclease III, nuclear ENST00000375734 NM_005168 RND3 Rho family GTPase 3 ENST00000311269 RNF190 ENST00000358395 NM_007219 RNF24 Ring finger protein 24 ENST00000339626 NM_005977 RNF6 Ring finger protein (C3H2C3 NM_183043 type) 6 NM_183044 NM_183045 ENST00000369485 RNGTT RNA guanylyltransferase and 5′- phosphatase ENST00000296255 NM_002950 RPN1 Ribophorin I ENST00000341844 RPS12 Ribosomal protein S12 ENST00000372360 RPS24 Ribosomal protein S24 ENST00000334205 NM_001006944.1 RPS6KA4 Ribosomal protein S6 kinase, NM_003942 90 kDa, polypeptide 4 ENST00000261991 RPS6KA5 Ribosomal protein S6 kinase, 90 kDa, polypeptide 5 ENST00000312629 RPS6KB2 Ribosomal protein S6 kinase, 70 kDa, polypeptide 2 ENST00000358328 NM_031464 RPS6KL1 Ribosomal protein S6 kinase-like 1 ENST00000246792 RRAS Related RAS viral (r-ras) oncogene homolog ENST00000258955 NM_018346 RSAD1 Radical S-adenosyl methionine domain containing 1 ENST00000276659 NM_178565 RSPO2 R-spondin 2 homolog (Xenopus laevis) ENST00000368317 NM_032784 RSPO3 R-spondin 3 homolog (Xenopus laevis) ENST00000369724 RWDD2 ENST00000367891 NM_001009598 RXRG Retinoid X receptor, gamma NM_006917 ENST00000367469 NM_015278 SASH1 SAM and SH3 domain containing 1 ENST00000368363 NM_005698 SCAMP3 Secretory carrier membrane NM_052837 protein 3 ENST00000019103 NM_002980 SCTR Secretin receptor ENST00000247020 SDF2 Stromal cell-derived factor 2 ENST00000360001 SDF4 Stromal cell derived factor 4 ENST00000215812 SEC14L3 SEC14-like 3 (S. cerevisiae) ENST00000264454 SEC22C SEC22 vesicle trafficking protein homolog C (S. cerevisiae) ENST00000379041 SEC61A2 Sec61 alpha 2 subunit (S. cerevisiae) ENST00000368868 NM_003944 SELENBP1 Selenium binding protein 1 ENST00000355853 SEMA4G Sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G ENST00000357599 NM_001031702 SEMA5B Sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5B ENST00000367516 SEN15_HUMAN ENST00000004980 SENP1_HUMAN ENST00000367104 SERAC1 Serine active site containing 1 ENST00000372563 NM_000354 SERPINA7 Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7 ENST00000221455 NM_007056 SFRS16 Splicing factor, arginine/serine- rich 16 ENST00000229390 SFRS9 Splicing factor, arginine/serine- rich 9 ENST00000355697 SFXN4_HUMAN ENST00000373277 NM_005489 SH2D3C SH2 domain containing 3C NM_170600 ENST00000350336 NM_016009 SH3GLB1 SH3-domain GRB2-like endophilin B1 ENST00000359782 SIRT5 Sirtuin (silent mating type information regulation 2 homolog) 5 (S. cerevisiae) ENST00000354161 SLC12A9 Solute carrier family 12 (potassium/chloride transporters), member 9 ENST00000318989 SLC16A10 Solute carrier family 16, member 10 (aromatic amino acid transporter) ENST00000308453 NM_001098486.1 SLC17A3 Solute carrier family 17 (sodium NM_006632 phosphate), member 3 ENST00000273173 SLC22A14 Solute carrier family 22 (organic cation transporter), member 14 ENST00000345033 NM_003058 SLC22A2 Solute carrier family 22 (organic cation transporter), member 2 ENST00000317881 SLC25A5 Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5 ENST00000361193 NM_173626 SLC26A11 Solute carrier family 26, member 11 ENST00000356119 NM_052961 SLC26A8 Solute carrier family 26, member 8 NM_138718 ENST00000306873 SLC30A1 Solute carrier family 30 (zinc transporter), member 1 ENST00000379343 SLC30A6 Solute carrier family 30 (zinc transporter), member 6 ENST00000217420 NM_080552 SLC32A1 Solute carrier family 32 (GABA vesicular transporter), member 1 ENST00000298681 NM_014579 SLC39A2 Solute carrier family 39 (zinc transporter), member 2 ENST00000380059 NM_032034 SLC4A11 Solute carrier family 4, sodium borate transporter, member 11 ENST00000260126 SLCO5A1 Solute carrier organic anion transporter family, member 5A1 ENST00000359345 NM_144990 SLFNL1 Schlafen-like 1 ENST00000332281 SNAI3 Snail homolog 3 (Drosophila) ENST00000348795 NM_003087 SNCG Synuclein, gamma (breast cancer-specific protein 1) ENST00000354725 SND1_HUMAN ENST00000290330 SNF8 SNF8, ESCRT-II complex subunit, homolog (S. cerevisiae) ENST00000374015 SNRPC Small nuclear ribonucleoprotein polypeptide C ENST00000244227 SNUT3_HUMAN ENST00000379516 NM_003100 SNX2 Sorting nexin 2 ENST00000344780 SNX21_HUMAN ENST00000251847 SNX23_HUMAN ENST00000264694 NM_031953 SNX25 Sorting nexin 25 ENST00000306121 NM_015976 SNX7 Sorting nexin 7 NM_152238 ENST00000302056 NM_004232 SOCS6 Suppressor of cytokine signaling 6 ENST00000373645 NM_001005176 SP140 SP140 nuclear body protein NM_007237.3 ENST00000282470 NM_004684 SPARCL1 SPARC-like 1 (mast9, hevin) ENST00000351008 NM_031955 SPATA16 Spermatogenesis associated 16 ENST00000289431 NM_006038 SPATA2 Spermatogenesis associated 2 ENST00000282074 SPBC25 ENST00000377104 SPRY2 Sprouty homolog 2 (Drosophila) ENST00000372739 NM_003127 SPTAN1 Spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) ENST00000379648 SRP19 Signal recognition particle 19 kDa ENST00000343379 NM_015558 SS18L1 Synovial sarcoma translocation NM_198935 gene on chromosome 18-like 1 ENST00000278742 NM_021978 ST14 Suppression of tumorigenicity 14 (colon carcinoma) ENST00000382009 NM_020860 STIM2 Stromal interaction molecule 2 ENST00000368625 STK32C Serine/threonine kinase 32C ENST00000220876 STMN2 Stathmin-like 2 ENST00000378577 STOML2 Stomatin (EPB72)-like 2 ENST00000298596 NM_152709.3 STOX1 Storkhead box 1 ENST00000374263 NM_022486 SUSD1 Sushi domain containing 1 ENST00000342784 SYDE1 Synapse defective 1, Rho GTPase, homolog 1 (C. elegans) ENST00000360448 SYTL3 Synaptotagmin-like 3 ENST00000369958 TAF13 TAF13 RNA polymerase II, TATA box binding protein (TBP)- associated factor, 18 kDa ENST00000380818 NM_001015892 TAF9 TAF9 RNA polymerase II, TATA NM_003187 box binding protein (TBP)- associated factor, 32 kDa ENST00000374895 NM_000544.3 TAP2 Transporter 2, ATP-binding NM_018833 cassette, sub-family B (MDR/TAP) ENST00000040877 NM_005646 TARBP1 TAR (HIV-1) RNA binding protein 1 ENST00000375371 NM_152232 TAS1R2 Taste receptor, type 1, member 2 ENST00000331710 NM_013254 TBK1 TANK-binding kinase 1 ENST00000230354 NM_003194 TBP TATA box binding protein ENST00000247219 NM_199047 TBPL2 TATA box binding protein like 2 ENST00000369431 NM_152380 TBX15 T-box 15 ENST00000309889 NM_003673 TCAP Titin-cap (telethonin) ENST00000282111 NM_031283 TCF7L1 Transcription factor 7-like 1 (T- cell specific, HMG-box) ENST00000373977 NM_001093728.1 TCP11 T-complex 11 (mouse) NM_018679 ENST00000335725 NM_001008744 TDP1 Tyrosyl-DNA phosphodiesterase 1 NM_018319 ENST00000372578 NM_031274.3 TEX13A Testis expressed 13A ENST00000274400 TF2H2_HUMAN ENST00000222543 NM_006528 TFPI2 Tissue factor pathway inhibitor 2 ENST00000261600 THOC1 THO complex 1 ENST00000264637 THRA Thyroid hormone receptor, alpha (erythroblastic leukemia viral (v- erb-a) oncogene homolog, avian) ENST00000297347 THRAP6 ENST00000288014 THTPA Thiamine triphosphatase ENST00000287814 NM_003256 TIMP4 TIMP metallopeptidase inhibitor 4 ENST00000296802 TIP1_HUMAN ENST00000311912 NM_016610 TLR8 Toll-like receptor 8 NM_138636 ENST00000370196 TLX1_HUMAN ENST00000294613 NM_032027.2 TM2D1 TM2 domain containing 1 ENST00000299705 TMED3 Transmembrane emp24 protein transport domain containing 3 ENST00000206380 TMEM101 Transmembrane protein 101 ENST00000216080 TMEM153 ENST00000292246 NM_018075 TMEM16K Transmembrane protein 16K ENST00000336702 NM_014807 TMEM24 Transmembrane protein 24 ENST00000297459 NM_153015 TMEM74 Transmembrane protein 74 ENST00000307216 NM_015497 TMEM87A Transmembrane protein 87A ENST00000300433 NM_153229 TMEM92 Transmembrane protein 92 ENST00000335572 NM_182559.2 TMPRSS12 Transmembrane protease, serine 12 ENST00000233143 NM_021103 TMSB10 Thymosin, beta 10 ENST00000297533 TMUB1 Transmembrane and ubiquitin- like domain containing 1 ENST00000264331 NM_001068.2 TOP2B Topoisomerase (DNA) II beta 180 kDa ENST00000373284 NM_001085347.1 TOR2A Torsin family 2, member A NM_130459 ENST00000301057 TP53I13 Tumor protein p53 inducible protein 13 ENST00000308422 NM_000547 TPO Thyroid peroxidase NM_175719 NM_175720 NM_175721 NM_175722 ENST00000367478 NM_003292.2 TPR Translocated promoter region (to activated MET oncogene) ENST00000340513 NM_012112 TPX2 TPX2, microtubule-associated, homolog (Xenopus laevis) ENST00000373887 NM_005658 TRAF1 TNF receptor-associated factor 1 ENST00000367023 TRAF3IP3 TRAF3 interacting protein 3 ENST00000297221 TRERF1 Transcriptional regulating factor 1 ENST00000357105 TREX1 Three prime repair exonuclease 1 ENST00000311762 NM_003301 TRHR Thyrotropin-releasing hormone receptor ENST00000274327 NM_001656 TRIM23 Tripartite motif-containing 23 NM_033227.2 NM_033228 ENST00000357530 NM_024114 TRIM48 Tripartite motif-containing 48 ENST00000380027 TRIM5 Tripartite motif-containing 5 ENST00000333149 NM_178125 TRIM50 Tripartite motif-containing 50 ENST00000360177 TRIM59 Tripartite motif-containing 59 ENST00000379705 NM_016179 TRPC4 Transient receptor potential cation channel, subfamily C, member 4 ENST00000277065 NM_001007470.1 TRPM3 Transient receptor potential NM_001007471.2 cation channel, subfamily M, NM_020952.4 member 3 NM_024971 NM_206945.3 NM_206946 NM_206947 NM_206948 ENST00000333213 NM_207346 TSEN54 TRNA splicing endonuclease 54 homolog (S. cerevisiae) ENST00000307180 NM_145003 TSNARE1 T-SNARE domain containing 1 ENST00000372003 NM_005727 TSPAN1 Tetraspanin 1 ENST00000375442 TSPYL2 TSPY-like 2 ENST00000382110 TTC15 Tetratricopeptide repeat domain 15 ENST00000334974 TUBGCP2 Tubulin, gamma complex associated protein 2 ENST00000216185 TXN2 Thioredoxin 2 ENST00000371626 NM_015913 TXNDC12 Thioredoxin domain containing 12 (endoplasmic reticulum) ENST00000369317 NM_006472 TXNIP Thioredoxin interacting protein ENST00000301944 TXNL6 ENST00000367926 NM_003115 UAP1 UDP-N-acteylglucosamine pyrophosphorylase 1 ENST00000340573 NM_004223 UBE2L6 Ubiquitin-conjugating enzyme NM_198183 E2L 6 ENST00000371076 NM_152489 UBE2U Ubiquitin-conjugating enzyme E2U (putative) ENST00000381764 UCHL1 Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) ENST00000337130 UGP2 UDP-glucose pyrophosphorylase 2 ENST00000268159 NM_001039675.1 UNC45A Unc-45 homolog A (C. elegans) NM_018671 ENST00000340926 NM_025154.3 UNC84A Unc-84 homolog A (C. elegans) ENST00000366829 NM_018974 UNC93A Unc-93 homolog A (C. elegans) ENST00000262946 NM_006830 UQCR Ubiquinol-cytochrome c reductase, 6.4 kDa subunit ENST00000335373 NM_006677.1 USP19 Ubiquitin specific peptidase 19 ENST00000304076 NM_005428 VAV1 Vav 1 guanine nucleotide exchange factor ENST00000313132 VDAC2 Voltage-dependent anion channel 2 ENST00000309422 VEGFB Vascular endothelial growth factor B ENST00000280193 NM_005429.2 VEGFC Vascular endothelial growth factor C ENST00000249330 NM_003378 VGF VGF nerve growth factor inducible ENST00000367244 NM_003381 VIP Vasoactive intestinal peptide NM_194435 ENST00000301774 VMD2 ENST00000331471 VMDL3_HUMAN ENST00000355155 VP13B_HUMAN ENST00000220509 NM_020857 VPS18 Vacuolar protein sorting 18 homolog (S. cerevisiae) ENST00000324849 VPS37A Vacuolar protein sorting 37 homolog A (S. cerevisiae) ENST00000369456 NM_024626 VTCN1 V-set domain containing T cell activation inhibitor 1 ENST00000233615 WBP1 WW domain binding protein 1 ENST00000381329 NM_014023 WDR37 WD repeat domain 37 ENST00000330317 WDR4 WD repeat domain 4 ENST00000378322 WDR8 WD repeat domain 8 ENST00000368664 WISP3 WNT1 inducible signaling pathway protein 3 ENST00000366753 NM_033131 WNT3A Wingless-type MMTV integration site family, member 3A ENST00000380713 WRB Tryptophan rich basic protein ENST00000313620 XP_292836.3 ENST00000372288 XP_931110.1 ENST00000383005 XP_932040.1 ENST00000309582 XP_935270.1 ENST00000255845 XP_937394.1 ENST00000388939 XP_937526.1 ENST00000378263 XP_942691.1 ENST00000378260 XP_942710.1 ENST00000323562 XP_943634.1 ENST00000331993 XP_944689.1 ENST00000303979 XP_944836.1 ENST00000367014 XR_000991.1 ENST00000380885 XR_001064.1 ENST00000282268 NM_003401 XRCC4 X-ray repair complementing NM_022406 defective repair in Chinese NM_022550 hamster cells 4 ENST00000300145 NM_033276.2 XRCC6BP1 XRCC6 binding protein 1 ENST00000339413 NM_001039671.1 YIF1B Yip1 interacting factor homolog NM_001039672 B (S. cerevisiae) NM_001039673.1 NM_033557 ENST00000204279 YPEL3 Yippee-like 3 (Drosophila) ENST00000317012 NM_024508 ZBED2 Zinc finger, BED-type containing 2 ENST00000291374 ZBTB8_HUMAN ENST00000218506 NM_144969 ZDHHC15 Zinc finger, DHHC-type containing 15 ENST00000216602 ZFYVE21 Zinc finger, FYVE domain containing 21 ENST00000339296 ZN621_HUMAN ENST00000358296 NM_173531.2 ZNF100 Zinc finger protein 100 ENST00000360371 ZNF124 Zinc finger protein 124 ENST00000343499 ZNF177 Zinc finger protein 177 ENST00000300823 NM_001032372.1 ZNF226 Zinc finger protein 226 NM_001032373.1 NM_001032374.1 NM_001032375.1 NM_015919.3 ENST00000377255 ZNF306 ENST00000361328 ZNF31 ENST00000372167 ZNF334 Zinc finger protein 334 ENST00000243644 NM_021632 ZNF350 Zinc finger protein 350 ENST00000361807 NM_145312 ZNF485 Zinc finger protein 485 ENST00000361113 NM_145295.2 ZNF627 Zinc finger protein 627 ENST00000358785 NM_024804 ZNF669 Zinc finger protein 669 ENST00000341976 NM_021916 ZNF70 Zinc finger protein 70 ENST00000293068 ZNFN1A3 ENST00000233331 ZNHIT4 Zinc finger, HIT type 4

TABLE 3 miR-27a targets identified by miRanda and L2L. Target Gene Accession No: Gene Name ADAMTS4 NM_005099.4 ADAM metallopeptidase with GI: 157427674 thrombospondin type 1 motif, 4 AHSG NM_001622.2 alpha-2-HS-glycoprotein GI: 156523969 ALPL NM_000478.3 alkaline phosphatase, liver/bone/kidney GI: 116734716 BMI1 NM_005180.5 BMI1 polycomb ring finger oncogene GI: 39725706 CHRD NM_003741.2 chordin GI: 30089979 DLX5 NM_005221.5 distal-less homeobox 5 GI: 84043959 HOXA13 NM_000522.3 homeobox A13 GI: 84452162 MATN1 NM_002379.2 matrilin 1, cartilage matrix protein GI: 13518035 MINPP1 NM_004897.2 multiple inositol polyphosphate GI: 19923760 histidine phosphatase, 1 PEX7 NM_000288.1 peroxisomal biogenesis factor 7 GI: 4505730 PRKRA NM_003690.3 protein kinase, interferon-inducible double GI: 32261293 stranded RNA dependent activator THRA NM_199334.2 thyroid hormone receptor, alpha GI: 46255056 (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) THRA NM_003250.4 thyroid hormone receptor, alpha GI: 40806158 (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)

TABLE 4 All targets of miR-489. RefSeq Accession Transcript ID Number Target Name Gene Name ENST00000263100 NM_130786 A1BG Alpha-1-B glycoprotein ENST00000389663 NM_015657 ABCA12 ATP-binding cassette, sub- NM_173076 family A (ABC1), member 12 ENST00000382055 NM_178559 ABCB5 ATP-binding cassette, sub- family B (MDR/TAP), member 5 ENST00000339718 NM_033226 ABCC12 ATP-binding cassette, sub- family C (CFTR/MRP), member 12 ENST00000334444 NM_001023587 ABCC5 ATP-binding cassette, sub- NM_005688.2 family C (CFTR/MRP), member 5 ENST00000295962 ABHD6 Abhydrolase domain containing 6 ENST00000308982 ACAD9 Acyl-Coenzyme A dehydrogenase family, member 9 ENST00000231909 NM_022899 ACTR8 ARP8 actin-related protein 8 homolog (yeast) ENST00000303536 ACYP2 Acylphosphatase 2, muscle type ENST00000256389 NM_003814 ADAM20 ADAM metallopeptidase domain 20 ENST00000335595 NM_003817 ADAM7 ADAM metallopeptidase domain 7 ENST00000352040 NM_030955 ADAMTS12 ADAM metallopeptidase with thrombospondin type 1 motif, 12 ENST00000299164 NM_139055 ADAMTS15 ADAM metallopeptidase with thrombospondin type 1 motif, 15 ENST00000380559 NM_001040272.4 ADAMTSL1 ADAMTS-like 1 NM_052866 NM_139238 NM_139264 ENST00000238561 ADCK1 AarF domain containing kinase 1 ENST00000349243 AGTR1 Angiotensin II receptor, type 1 ENST00000273784 NM_001622 AHSG Alpha-2-HS-glycoprotein ENST00000367601 NM_016108 AIG1 Androgen-induced 1 ENST00000373176 NM_000476 AK1 Adenylate kinase 1 ENST00000267584 NM_152327 AK7 Adenylate kinase 7 ENST00000228850 NM_006422 AKAP3 A kinase (PRKA) anchor protein 3 ENST00000358526 NM_003886 AKAP4 A kinase (PRKA) anchor protein 4 NM_139289 ENST00000285930 AKR1B1 Aldo-keto reductase family 1, member B1 (aldose reductase) ENST00000339618 NM_000382 ALDH3A2 Aldehyde dehydrogenase 3 NM_001031806 family, member A2 ENST00000007633 NM_000694.2 ALDH3B1 Aldehyde dehydrogenase 3 NM_001030010.1 family, member B1 ENST00000338110 ALDOA_HUMAN ENST00000374978 NM_033087 ALG2 Asparagine-linked glycosylation 2 homolog (S. cerevisiae, alpha- 1,3-mannosyltransferase) ENST00000239891 ALG5 Asparagine-linked glycosylation 5 homolog (S. cerevisiae, dolichyl-phosphate beta- glucosyltransferase) ENST00000216489 NM_006020 ALKBH1 AlkB, alkylation repair homolog 1 (E. coli) ENST00000378840 ALKBH3 AlkB, alkylation repair homolog 3 (E. coli) ENST00000380490 ALOX5AP Arachidonate 5-lipoxygenase- activating protein ENST00000383037 NM_001143 AMELY Amelogenin, Y-linked ENST00000338852 AMY2B Amylase, alpha 2B (pancreatic) ENST00000354910 NM_015391 ANAPC13 Anaphase promoting complex subunit 13 ENST00000304704 NM_002937 ANG Angiogenin, ribonuclease, NM_194430 RNase A family, 5 NM_194431 ENST00000367629 NM_004673 ANGPTL1 Angiopoietin-like 1 ENST00000373815 NM_001149 ANK3 Ankyrin 3, node of Ranvier NM_020987 (ankyrin G) ENST00000357927 ANKRD18A Ankyrin repeat domain 18A ENST00000322980 NM_173505 ANKRD29 Ankyrin repeat domain 29 ENST00000296511 NM_001154 ANXA5 Annexin A5 ENST00000291439 AP1M1 Adaptor-related protein complex 1, mu 1 subunit ENST00000250244 NM_005498.3 AP1M2 Adaptor-related protein complex 1, mu 2 subunit ENST00000337619 NM_001283.3 AP1S1 Adaptor-related protein complex NM_057089.2 1, sigma 1 subunit ENST00000334271 NM_001039569.1 AP1S3 Adaptor-related protein complex 1, sigma 3 subunit ENST00000263270 AP2S1 Adaptor-related protein complex 2, sigma 1 subunit ENST00000278359 APIP APAF1 interacting protein ENST00000375918 NM_019101 APOM Apolipoprotein M ENST00000315596 APRIN ENST00000368087 ARG1 Arginase, liver ENST00000300901 ARHGAP23 Rho GTPase activating protein 23 ENST00000273258 NM_006407 ARL6IP5 ADP-ribosylation-like factor 6 interacting protein 5 ENST00000305242 NM_018076 ARMC4 Armadillo repeat containing 4 ENST00000349321 ART3 ADP-ribosyltransferase 3 ENST00000389601 NM_130387 ASB14 Ankyrin repeat and SOCS box- containing 14 ENST00000263634 NM_016115 ASB3 Ankyrin repeat and SOCS box- NM_145863 containing 3 ENST00000266744 ASCL1 Achaete-scute complex homolog 1 (Drosophila) ENST00000375689 NM_015338 ASXL1 Additional sex combs like 1 (Drosophila) ENST00000264110 ATF2 Activating transcription factor 2 ENST00000317868 NM_032852 ATG4C ATG4 autophagy related 4 NM_178221 homolog C (S. cerevisiae) ENST00000309469 NM_032885 ATG4D ATG4 autophagy related 4 homolog D (S. cerevisiae) ENST00000286371 ATP1B3 ATPase, Na+/K+ transporting, beta 3 polypeptide ENST00000349466 NM_001001344 ATP2B3 ATPase, Ca++ transporting, NM_021949 plasma membrane 3 ENST00000284727 NM_001002258 ATP5G3 ATP synthase, H+ transporting, NM_001689 mitochondrial F0 complex, subunit C3 (subunit 9) ENST00000330342 NM_012463 ATP6V0A2 ATPase, H+ transporting, lysosomal V0 subunit a2 ENST00000290949 ATP6V0D1 ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d1 ENST00000335514 ATPIF1 ATPase inhibitory factor 1 ENST00000377526 AUP1 Ancient ubiquitous protein 1 ENST00000382956 AXIN1 Axin 1 ENST00000367998 B4GALT3 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 3 ENST00000375372 BARX1 BARX homeobox 1 ENST00000375842 BAT5 HLA-B associated transcript 5 ENST00000378455 NM_017745 BCOR BCL6 co-repressor NM_020926 ENST00000296424 NM_020139 BDH2 3-hydroxybutyrate dehydrogenase, type 2 ENST00000372677 BEX2 Brain expressed X-linked 2 ENST00000372645 BEX3_HUMAN ENST00000227758 NM_001166 BIRC2 Baculoviral IAP repeat- containing 2 ENST00000367807 NM_003666 BLZF1 Basic leucine zipper nuclear factor 1 (JEM-1) ENST00000265624 BMP7 Bone morphogenetic protein 7 (osteogenic protein 1) ENST00000349552 NM_174897 BPIL3 Bactericidal/permeability- increasing protein-like 3 ENST00000354807 NM_006085.4 BPNT1 3′(2′), 5′-bisphosphate nucleotidase 1 ENST00000220659 BRF2 BRF2, subunit of RNA polymerase III transcription initiation factor, BRF1-like ENST00000339775 NM_006806 BTG3 BTG family, member 3 ENST00000289361 BTN3A1 Butyrophilin, subfamily 3, member A1 ENST00000244519 BTN3A3 Butyrophilin, subfamily 3, member A3 ENST00000230340 BYSL Bystin-like ENST00000337623 NM_015608 C10orf137 Chromosome 10 open reading frame 137 ENST00000331772 NM_001031709 C10orf59 Chromosome 10 open reading NM_018363 frame 59 ENST00000374157 C10orf73 Chromosome 10 open reading frame 73 ENST00000368887 C10orf89 ENST00000333254 NM_198515 C10orf96 Chromosome 10 open reading frame 96 ENST00000378615 C11orf49 Chromosome 11 open reading frame 49 ENST00000261191 NM_018164 C12orf11 Chromosome 12 open reading frame 11 ENST00000261700 C14orf166 Chromosome 14 open reading frame 166 ENST00000256545 C15orf24 Chromosome 15 open reading frame 24 ENST00000311880 C17orf66 Chromosome 17 open reading frame 66 ENST00000389005 NM_018553 C17orf85 Chromosome 17 open reading frame 85 ENST00000333234 NM_031446 C18orf21 Chromosome 18 open reading frame 21 ENST00000300227 NM_198995 C18orf34 Chromosome 18 open reading frame 34 ENST00000367910 NM_178550.4 C1orf110 Chromosome 1 open reading frame 110 ENST00000371760 C1orf185 Chromosome 1 open reading frame 185 ENST00000371980 NM_001013615 C1orf190 Chromosome 1 open reading frame 190 ENST00000368790 C1orf42 ENST00000331283 C21orf119 Chromosome 21 open reading frame 119 ENST00000266155 NM_031444 C22orf13 Chromosome 22 open reading frame 13 ENST00000295049 C2orf11 ENST00000273037 C3orf31 Chromosome 3 open reading frame 31 ENST00000318887 NM_173824 C3orf38 Chromosome 3 open reading frame 38 ENST00000344697 NM_032806 C3orf39 Chromosome 3 open reading frame 39 ENST00000341199 C5orf25 Chromosome 5 open reading frame 25 ENST00000244558 C6orf130 Chromosome 6 open reading frame 130 ENST00000369552 NM_001031743 C6orf165 Chromosome 6 open reading NM_178823 frame 165 ENST00000316149 C6orf66 Chromosome 6 open reading frame 66 ENST00000368596 C6orf78 ENST00000234643 NM_000066 C8B Complement component 8, beta polypeptide ENST00000375117 C9orf156 Chromosome 9 open reading frame 156 ENST00000256925 CABL1_HUMAN ENST00000325656 NM_145200 CABP4 Calcium binding protein 4 ENST00000350061 NM_000720 CACNA1D Calcium channel, voltage- dependent, L type, alpha 1D subunit ENST00000263942 NM_000069 CACNA1S Calcium channel, voltage- dependent, L type, alpha 1S subunit ENST00000329008 NM_001017440 CALN1 Calneuron 1 NM_031468 ENST00000359414 CAPN13 Calpain 13 ENST00000251973 NM_014550 CARD10 Caspase recruitment domain family, member 10 ENST00000309710 CARD14 Caspase recruitment domain family, member 14 ENST00000296777 CART_HUMAN ENST00000247026 CCDC55 Coiled-coil domain containing 55 ENST00000320516 NM_033124 CCDC65 Coiled-coil domain containing 65 ENST00000321945 NM_139076 CCDC98 Coiled-coil domain containing 98 ENST00000358813 NM_004591 CCL20 Chemokine (C-C motif) ligand 20 ENST00000250151 CCL4 Chemokine (C-C motif) ligand 4 ENST00000378569 CCL7 Chemokine (C-C motif) ligand 7 ENST00000225840 CCL8 Chemokine (C-C motif) ligand 8 ENST00000376042 NM_033031 CCNB3 Cyclin B3 NM_033670 ENST00000360054 NM_001039577 CCNL2 Cyclin L2 NM_030937 ENST00000299300 NM_006431 CCT2 Chaperonin containing TCP1, subunit 2 (beta) ENST00000258091 NM_001009570.1 CCT7 Chaperonin containing TCP1, NM_006429.2 subunit 7 (eta) ENST00000368169 NM_001765 CD1C CD1c molecule ENST00000354397 NM_021155 CD209 CD209 molecule ENST00000368034 NM_016382 CD244 CD244 molecule, natural killer cell receptor 2B4 ENST00000262262 NM_001082618.1 CD33 CD33 molecule NM_001772 ENST00000226279 CD38 CD38 molecule ENST00000381180 CD99 CD99 molecule ENST00000229265 CDCA3 Cell division cycle associated 3 ENST00000336219 CDCA4_HUMAN ENST00000268794 NM_004360 CDH1 Cadherin 1, type 1, E-cadherin (epithelial) ENST00000382239 NM_006727 CDH10 Cadherin 10, type 2 (T2- cadherin) ENST00000268603 NM_001797 CDH11 Cadherin 11, type 2, OB- cadherin (osteoblast) ENST00000219789 NM_006319 CDIPT CDP-diacylglycerol--inositol 3- phosphatidyltransferase (phosphatidylinositol synthase) ENST00000361279 CDKN2A Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) ENST00000262662 CDKN2C Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) ENST00000006724 NM_006890 CEACAM7 Carcinoembryonic antigen- related cell adhesion molecule 7 ENST00000331437 NM_031890 CECR6 Cat eye syndrome chromosome region, candidate 6 ENST00000379037 NM_030649 CENTB5 Centaurin, beta 5 ENST00000373855 NM_007018 CEP110 Centrosomal protein 110 kDa ENST00000375002 CF010_HUMAN ENST00000370318 CF150_HUMAN ENST00000355693 CHCHD8 Coiled-coil-helix-coiled-coil-helix domain containing 8 ENST00000361293 NM_004284 CHD1L Chromodomain helicase DNA binding protein 1-like ENST00000309818 NM_001042572.2 CHD2 Chromodomain helicase DNA NM_001271 binding protein 2 ENST00000266880 CHFR Checkpoint with forkhead and ring finger domains ENST00000035307 CHGUT_HUMAN ENST00000342610 CHRD Chordin ENST00000263671 NM_015424 CHRDL2 Chordin-like 2 ENST00000276410 NM_004198 CHRNA6 Cholinergic receptor, nicotinic, alpha 6 ENST00000370397 CHUK Conserved helix-loop-helix ubiquitous kinase ENST00000381895 CI068_HUMAN ENST00000377773 CI105_HUMAN ENST00000317358 CJ055_HUMAN ENST00000342366 NM_000084 CLCN5 Chloride channel 5 (nephrolithiasis 2, X-linked, Dent disease) ENST00000328796 NM_021195 CLDN6 Claudin 6 ENST00000300107 CLPX ClpX caseinolytic peptidase X homolog (E. coli) ENST00000360535 CLR59_HUMAN ENST00000263200 NM_007098.2 CLTCL1 Clathrin, heavy chain-like 1 ENST00000380446 NM_001831 CLU Clusterin NM_203339.1 ENST00000338387 NM_014410.4 CLUL1 Clusterin-like 1 (retinal) NM_199167.1 ENST00000229329 CMAS Cytidine monophosphate N- acetylneuraminic acid synthetase ENST00000306954 CN142_HUMAN ENST00000303904 COPS6 COP9 constitutive photomorphogenic homolog subunit 6 (Arabidopsis) ENST00000229251 NM_016319 COPS7A COP9 constitutive photomorphogenic homolog subunit 7A (Arabidopsis) ENST00000300452 COQ4 Coenzyme Q4 homolog (S. cerevisiae) ENST00000314133 NM_004074 COX8A Cytochrome c oxidase subunit 8A (ubiquitous) ENST00000264613 NM_000096 CP Ceruloplasmin (ferroxidase) ENST00000296046 NM_001870 CPA3 Carboxypeptidase A3 (mast cell) ENST00000359703 CPE Carboxypeptidase E ENST00000266679 NM_007007 CPSF6 Cleavage and polyadenylation specific factor 6, 68 kDa ENST00000299529 CRABP1 Cellular retinoic acid binding protein 1 ENST00000354577 CRSP3 ENST00000353151 NM_001891 CSN2 Casein beta ENST00000361804 CSPG6 ENST00000370938 NM_001902 CTH Cystathionase (cystathionine NM_153742 gamma-lyase) ENST00000330295 NM_138455 CTHRC1 Collagen triple helix repeat containing 1 ENST00000375943 CTRC Chymotrypsin C (caldecrin) ENST00000217131 NM_001336 CTSZ Cathepsin Z ENST00000346329 NM_005231.2 CTTN Cortactin NM_138565 ENST00000382705 CU063_HUMAN ENST00000310513 CUGBP1 CUG triplet repeat, RNA binding protein 1 ENST00000310806 CV106_HUMAN ENST00000371594 NM_022101 CXorf56 Chromosome X open reading frame 56 ENST00000302517 NM_016463.6 CXXC5 CXXC finger 5 ENST00000371904 NM_000778 CYP4A11 Cytochrome P450, family 4, subfamily A, polypeptide 11 ENST00000250498 NM_001344 DAD1 Defender against cell death 1 ENST00000264161 NM_001349 DARS Aspartyl-tRNA synthetase ENST00000369563 NM_022836 DCLRE1B DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae) ENST00000263576 NM_013264.2 DDX25 DEAD (Asp-Glu-Ala-Asp) box polypeptide 25 ENST00000382697 NM_001925 DEFA4 Defensin, alpha 4, corticostatin ENST00000362033 NM_004401 DFFA DNA fragmentation factor, NM_213566 45 kDa, alpha polypeptide ENST00000264057 NM_003648.2 DGKD Diacylglycerol kinase, delta NM_152879 130 kDa ENST00000346603 DHRS7B Dehydrogenase/reductase (SDR family) member 7B ENST00000358290 DHRS8 ENST00000199320 DIMH_HUMAN ENST00000366636 DISC1 Disrupted in schizophrenia 1 ENST00000346964 NM_001098424.1 DLG1 Discs, large homolog 1 NM_004087 (Drosophila) ENST00000190165 NM_021240 DMRT3 Doublesex and mab-3 related transcription factor 3 ENST00000082259 NM_020877 DNAH2 Dynein, axonemal, heavy chain 2 ENST00000376795 DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3 ENST00000359526 NM_001379 DNMT1 DNA (cytosine-5-)- methyltransferase 1 ENST00000382345 DOCK8_HUMAN ENST00000371403 NM_018431 DOK5 Docking protein 5 ENST00000382713 DOK6_HUMAN ENST00000268795 DPEP2 Dipeptidase 2 ENST00000360534 NM_001935 DPP4 Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2) ENST00000342856 NM_181787 DPY19L4 Dpy-19-like 4 (C. elegans) ENST00000370192 NM_000110 DPYD Dihydropyrimidine dehydrogenase ENST00000338492 NM_006426 DPYSL4 Dihydropyrimidinase-like 4 ENST00000382465 NM_000798 DRD5 Dopamine receptor D5 ENST00000374395 DSCR1L2 ENST00000377846 DSTN Destrin (actin depolymerizing factor) ENST00000267837 DUOX2 Dual oxidase 2 ENST00000288943 NM_004418 DUSP2 Dual specificity phosphatase 2 ENST00000372199 NM_032372 DYDC2 DPY30 domain containing 2 ENST00000375735 NM_001080463.1 DYNC2H1 Dynein, cytoplasmic 2, heavy chain 1 ENST00000240343 DYNLL2 Dynein, light chain, LC8-type 2 ENST00000372497 EBNA1BP2 EBNA1 binding protein 2 ENST00000372979 NM_007265 ECD Ecdysoneless homolog (Drosophila) ENST00000253392 NM_021783 EDA2R Ectodysplasin A2 receptor ENST00000309311 NM_001961 EEF2 Eukaryotic translation elongation factor 2 ENST00000337611 NM_001039348 EFEMP1 EGF-containing fibulin-like NM_001039349 extracellular matrix protein 1 NM_004105 ENST00000382374 EFHA1 EF-hand domain family, member A1 ENST00000344838 NM_144715 EFHB EF-hand domain family, member B ENST00000250457 NM_022073 EGLN3 Egl nine homolog 3 (C. elegans) ENST00000253039 NM_001415 EIF2S3 Eukaryotic translation initiation factor 2, subunit 3 gamma, 52 kDa ENST00000380512 EIF4A1 Eukaryotic translation initiation factor 4A, isoform 1 ENST00000269466 NM_018696 ELAC1 ElaC homolog 1 (E. coli) ENST00000379498 ELF1 E74-like factor 1 (ets domain transcription factor) ENST00000163344 NM_022821 ELOVL1 Elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 1 ENST00000295206 NM_001426 EN1 Engrailed homeobox 1 ENST00000361674 ENK13_HUMAN ENST00000254928 ERAL1 Era G-protein-like 1 (E. coli) ENST00000376107 ERCC3 Excision repair cross- complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing) ENST00000314992 NM_152596 EXDL1 Exonuclease 3′-5′ domain-like 1 ENST00000381295 NM_001024924 EXOC1 Exocyst complex component 1 NM_018261 NM_178237 ENST00000300005 NM_080663 EXOD1 Exonuclease domain containing 1 ENST00000370880 NM_016046 EXOSC1 Exosome component 1 ENST00000319211 NM_001992 F2R Coagulation factor II (thrombin) receptor ENST00000371780 NM_007051 FAF1 Fas (TNFRSF6) associated factor 1 ENST00000306378 FALZ_HUMAN ENST00000373084 FAM102A Family with sequence similarity 102, member A ENST00000361723 NM_022074 FAM111A Family with sequence similarity NM_198847 111, member A ENST00000264344 FAM13A1 Family with sequence similarity 13, member A1 ENST00000359943 NM_001040020 FAM3C Family with sequence similarity NM_014888 3, member C ENST00000369796 FAM40A Family with sequence similarity 40, member A ENST00000380274 NM_012135 FAM50B Family with sequence similarity 50, member B ENST00000372570 NM_173642 FAM80A Family with sequence similarity 80, member A ENST00000297530 FASTK Fas-activated serine/threonine kinase ENST00000368178 NM_030764 FCRL2 Fc receptor-like 2 NM_138738 ENST00000359263 NM_013451.2 FER1L3 Fer-1-like 3, myoferlin (C. elegans) NM_133337.1 ENST00000373535 NM_173558 FGD2 FYVE, RhoGEF and PH domain containing 2 ENST00000228837 NM_020996 FGF6 Fibroblast growth factor 6 ENST00000382333 NM_005130 FGFBP1 Fibroblast growth factor binding protein 1 ENST00000344213 FHL2 Four and a half LIM domains 2 ENST00000325888 NM_001458.3 FLNC Filamin C, gamma (actin binding protein 280) ENST00000008553 NM_001002294 FMO3 Flavin containing NM_006894 monooxygenase 3 ENST00000343844 NM_001014986 FOLH1 Folate hydrolase (prostate- NM_004476 specific membrane antigen) 1 ENST00000263578 FOXRED1 FAD-dependent oxidoreductase domain containing 1 ENST00000305531 NM_001017929 FRMPD2 FERM and PDZ domain NM_001018071 containing 2 NM_152428 ENST00000287474 NM_001013660 FRRS1 Ferric-chelate reductase 1 ENST00000265825 FSCN3 Fascin homolog 3, actin- bundling protein, testicular (Strongylocentrotus purpuratus) ENST00000304421 NM_000145 FSHR Follicle stimulating hormone NM_181446 receptor ENST00000379164 NM_020116 FSTL5 Follistatin-like 5 ENST00000367586 NM_032020 FUCA2 Fucosidase, alpha-L-2, plasma ENST00000254108 FUS Fusion (involved in t(12; 16) in malignant liposarcoma) ENST00000303225 NM_000149 FUT3 Fucosyltransferase 3 NM_001097639.1 (galactoside 3(4)-L- NM_001097640.1 fucosyltransferase, Lewis blood NM_001097641.1 group) ENST00000286955 NM_000150 FUT6 Fucosyltransferase 6 (alpha NM_001040701.1 (1,3) fucosyltransferase) ENST00000326575 NM_002035 FVT1 Follicular lymphoma variant translocation 1 ENST00000259271 GAD2 Glutamate decarboxylase 2 (pancreatic islets and brain, 65 kDa) ENST00000376665 NM_002049 GATA1 GATA binding protein 1 (globin transcription factor 1) ENST00000370545 GATA5 GATA binding protein 5 ENST00000233612 NM_012198 GCA Grancalcin, EF-hand calcium binding protein ENST00000255945 NM_018326 GIMAP4 GTPase, IMAP family member 4 ENST00000342280 NM_002060 GJA4 Gap junction protein, alpha 4, 37 kDa ENST00000377938 GKN1 Gastrokine 1 ENST00000306497 GLPK3_HUMAN ENST00000278400 NM_005838 GLYAT Glycine-N-acyltransferase NM_201648 ENST00000380251 NM_002069 GNAI1 Guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 ENST00000378609 NM_002074 GNB1 Guanine nucleotide binding protein (G protein), beta polypeptide 1 ENST00000261837 NM_006578.3 GNB5 Guanine nucleotide binding NM_016194 protein (G protein), beta 5 ENST00000335281 NM_053064 GNG2 Guanine nucleotide binding protein (G protein), gamma 2 ENST00000373062 GNL2 Guanine nucleotide binding protein-like 2 (nucleolar) ENST00000359187 GOG8A_HUMAN ENST00000381436 NM_005288 GPR12 G protein-coupled receptor 12 ENST00000367838 GPR161 G protein-coupled receptor 161 ENST00000335866 NM_001001549.1 GRB10 Growth factor receptor-bound NM_001001550.1 protein 10 NM_001001555.1 NM_005311.3 ENST00000381001 NM_001098477.1 GRSF1 G-rich RNA sequence binding NM_002092.3 factor 1 ENST00000341272 GSN Gelsolin (amyloidosis, Finnish type) ENST00000219627 NM_002094.2 GSPT1 G1 to S phase transition 1 ENST00000375981 NM_018094 GSPT2 G1 to S phase transition 2 ENST00000369831 GSTM2 Glutathione S-transferase M2 (muscle) ENST00000261195 NM_021957 GYS2 Glycogen synthase 2 (liver) ENST00000378789 NM_017545 HAO1 Hydroxyacid oxidase (glycolate oxidase) 1 ENST00000336133 HCC1_HUMAN ENST00000376800 NM_005844 HCG9 HLA complex group 9 ENST00000368632 NM_001527.2 HDAC2 Histone deacetylase 2 ENST00000264173 HEAT1_HUMAN ENST00000058691 HEBP2 Heme binding protein 2 ENST00000261609 NM_004667 HERC2 Hect domain and RLD 2 ENST00000296575 NM_022475 HHIP Hedgehog interacting protein ENST00000274787 HIGD2A HIG1 domain family, member 2A ENST00000377781 NM_021063 HIST1H2BD Histone cluster 1, H2bd NM_138720 ENST00000289352 HIST1H4D Histone cluster 1, H4d ENST00000361427 NM_005517 HMGN2 High-mobility group nucleosomal binding domain 2 ENST00000377575 NM_006353 HMGN4 High mobility group nucleosomal binding domain 4 ENST00000313093 NM_012292 HMHA1 Histocompatibility (minor) HA-1 ENST00000358715 NM_012484 HMMR Hyaluronan-mediated motility NM_012485 receptor (RHAMM) ENST00000313173 HOXD8 Homeobox D8 ENST00000375000 NM_016287 HP1BP3 Heterochromatin protein 1, binding protein 3 ENST00000370027 NM_024747 HPS6 Hermansky-Pudlak syndrome 6 ENST00000381418 HR Hairless homolog (mouse) ENST00000369413 HSD3B1 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 ENST00000369416 HSD3B2 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 ENST00000375650 HSPA1A Heat shock 70 kDa protein 1A ENST00000375653 HSPA1L Heat shock 70 kDa protein 1-like ENST00000304298 NM_080659 HSPB2 Heat shock 27 kDa protein 2 ENST00000258400 NM_000867 HTR2B 5-hydroxytryptamine (serotonin) receptor 2B ENST00000223026 NM_012269 HYAL4 Hyaluronoglucosaminidase 4 ENST00000240652 NM_000415 IAPP Islet amyloid polypeptide ENST00000371580 NM_004969 IDE Insulin-degrading enzyme ENST00000368132 NM_005531 IFI16 Interferon, gamma-inducible protein 16 ENST00000380206 NM_000605 IFNA2 Interferon, alpha 2 ENST00000229135 NM_000619 IFNG Interferon, gamma ENST00000357896 IFT20 Intraflagellar transport 20 homolog (Chlamydomonas) ENST00000270800 NM_021258 IL22RA1 Interleukin 22 receptor, alpha 1 ENST00000254636 IMMT Inner membrane protein, mitochondrial (mitofilin) ENST00000193391 NM_016247 IMPG2 Interphotoreceptor matrix proteoglycan 2 ENST00000338450 NM_005537 ING1 Inhibitor of growth family, NM_198217 member 1 NM_198218 NM_198219 ENST00000372343 NM_014652 IPO13 Importin 13 ENST00000360635 ITBP1_HUMAN ENST00000320640 NM_030790 ITFG1 Integrin alpha FG-GAP repeat containing 1 ENST00000339307 NM_000885.4 ITGA4 Integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA- 4 receptor) ENST00000222573 NM_002214 ITGB8 Integrin, beta 8 ENST00000295321 NM_017969 IWS1 IWS1 homolog (S. cerevisiae) ENST00000327520 JHD2C_HUMAN ENST00000240874 NM_001024660.2 KALRN Kalirin, RhoGEF kinase NM_003947 NM_007064 ENST00000377843 KC1A_HUMAN ENST00000290310 NM_172201 KCNE2 Potassium voltage-gated channel, Isk-related family, member 2 ENST00000381593 NM_002236 KCNF1 Potassium voltage-gated channel, subfamily F, member 1 ENST00000366621 KCNK1 Potassium channel, subfamily K, member 1 ENST00000303015 KCNK9 Potassium channel, subfamily K, member 9 ENST00000372443 NM_001014797.1 KCNMA1 Potassium large conductance NM_002247 calcium-activated channel, subfamily M, alpha member 1 ENST00000359963 KCNMB3L ENST00000264773 NM_021614 KCNN2 Potassium intermediate/small NM_170775.1 conductance calcium-activated channel, subfamily N, member 2 ENST00000382267 KDELR2 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 ENST00000335817 NM_014656 KIAA0040 KIAA0040 ENST00000264214 NM_015047 KIAA0090 KIAA0090 ENST00000297423 NM_001080394.1 KIAA0146 KIAA0146 ENST00000318709 KIAA0241 KIAA0241 ENST00000372442 NM_031207 KIAA0467 KIAA0467 ENST00000322335 NM_015229.3 KIAA0664 KIAA0664 ENST00000236980 KIAA0971 ENST00000242315 NM_015297.1 KIAA1045 KIAA1045 ENST00000297222 NM_152748 KIAA1324L KIAA1324-like ENST00000329923 NM_138346 KIAA2013 KIAA2013 ENST00000335044 NM_022342 KIF9 Kinesin family member 9 NM_182902 NM_182903 ENST00000367769 NM_014970 KIFAP3 Kinesin-associated protein 3 ENST00000381763 KKCC1_HUMAN ENST00000359358 NM_020805 KLHL14 Kelch-like 14 (Drosophila) ENST00000265023 NM_000893 KNG1 Kininogen 1 NM_001102416.1 ENST00000375773 NM_001032998 KYNU Kynureninase (L-kynurenine NM_003937 hydrolase) ENST00000381167 LAPTM4A Lysosomal-associated protein transmembrane 4 alpha ENST00000368787 NM_032563 LCE3D Late cornified envelope 3D ENST00000368789 NM_178435 LCE3E Late cornified envelope 3E ENST00000368791 NM_178438 LCE5A Late cornified envelope 5A ENST00000371748 NM_014564 LHX3 LIM homeobox 3 NM_178138 ENST00000316300 NM_005577.2 LPA Lipoprotein, Lp(a) ENST00000306688 NM_144999 LRRC45 Leucine rich repeat containing 45 ENST00000269025 LRRC46 Leucine rich repeat containing 46 ENST00000260382 NM_017691 LRRC49 Leucine rich repeat containing 49 ENST00000343742 LRRK2_HUMAN ENST00000228740 LTA4H Leukotriene A4 hydrolase ENST00000264265 NM_020169 LXN Latexin ENST00000219345 LYPLA3 Lysophospholipase 3 (lysosomal phospholipase A2) ENST00000285879 NM_005462 MAGEC1 Melanoma antigen family C, 1 ENST00000347546 NM_014599 MAGED2 Melanoma antigen family D, 2 NM_177433 NM_201222 ENST00000354489 NM_005906 MAK Male germ cell-associated kinase ENST00000369293 NM_024641 MANEA Mannosidase, endo-alpha ENST00000373045 NM_001031740.1 MANEAL Mannosidase, endo-alpha-like NM_152496 ENST00000307102 NM_002755 MAP2K1 Mitogen-activated protein kinase kinase 1 ENST00000354570 NM_003980 MAP7 Microtubule-associated protein 7 ENST00000374189 MAPK8 Mitogen-activated protein kinase 8 ENST00000347470 NM_002752 MAPK9 Mitogen-activated protein NM_139068.1 kinase 9 NM_139069.1 NM_139070 ENST00000329421 MARCKSL1 MARCKS-like 1 ENST00000376973 NM_006610 MASP2 Mannan-binding lectin serine NM_139208 peptidase 2 ENST00000359787 MB Myoglobin ENST00000370578 NM_001099855.1 MCF2 MCF.2 cell line derived NM_005369 transforming sequence ENST00000265056 NM_004526 MCM2 Minichromosome maintenance complex component 2 ENST00000233114 MDH1 Malate dehydrogenase 1, NAD (soluble) ENST00000359803 MDK Midkine (neurite growth- promoting factor 2) ENST00000346108 NM_005587.1 MEF2A Myocyte enhancer factor 2A ENST00000298048 NM_014791 MELK Maternal embryonic leucine zipper kinase ENST00000381290 NM_005926 MFAP1 Microfibrillar-associated protein 1 ENST00000228938 NM_000900 MGP Matrix Gla protein ENST00000379614 MICAL2 Microtubule associated monoxygenase, calponin and LIM domain containing 2 ENST00000317552 NM_000381 MID1 Midline 1 (Opitz/BBB syndrome) NM_001098624.1 NM_033290 ENST00000296597 MIMIT_HUMAN ENST00000388758 MKLN1 Muskelin 1, intracellular mediator containing kelch motifs ENST00000377052 MLLT10 Myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 10 ENST00000374259 MLLT7 ENST00000264605 NM_001042467.1 MLPH Melanophilin NM_024101 ENST00000182377 NM_018099 MLSTD1 Male sterility domain containing 1 ENST00000246912 MLX MAX-like protein X ENST00000260227 MMP7 Matrix metallopeptidase 7 (matrilysin, uterine) ENST00000370782 MMS19L ENST00000340556 NM_194270 MORN2 MORN repeat containing 2 ENST00000370778 NM_019556 MOSPD1 Motile sperm domain containing 1 ENST00000245959 MPIP2_HUMAN ENST00000332314 MRGPRG MAS-related GPR, member G ENST00000371785 MRPS2 Mitochondrial ribosomal protein S2 ENST00000310776 MRPS22 Mitochondrial ribosomal protein S22 ENST00000313608 MRPS23 Mitochondrial ribosomal protein S23 ENST00000272418 MRPS5 Mitochondrial ribosomal protein S5 ENST00000016913 NM_017716 MS4A12 Membrane-spanning 4- domains, subfamily A, member 12 ENST00000281047 MSGN1 Mesogenin 1 ENST00000360270 NM_002444 MSN Moesin ENST00000249442 NM_001006635.1 MTX2 Metaxin 2 NM_006554 ENST00000308110 MUS81 MUS81 endonuclease homolog (S. cerevisiae) ENST00000274813 MUT Methylmalonyl Coenzyme A mutase ENST00000301415 NM_001077186.1 MYH14 Myosin, heavy chain 14 NM_024729.3 ENST00000349606 NM_013262 MYLIP Myosin regulatory light chain interacting protein ENST00000358212 NM_000259.2 MYO5A Myosin VA (heavy chain 12, myoxin) ENST00000259021 NM_007067 MYST2 MYST histone acetyltransferase 2 ENST00000360149 NM_018257 MYT1 Myelin transcription factor 1 ENST00000202831 NCKX6_HUMAN ENST00000359003 NM_014071 NCOA6 Nuclear receptor coactivator 6 ENST00000274137 NDUFS6 NADH dehydrogenase (ubiquinone) Fe—S protein 6, 13 kDa (NADH-coenzyme Q reductase) ENST00000318388 NDUFV2 NADH dehydrogenase (ubiquinone) flavoprotein 2, 24 kDa ENST00000373599 NEK6 NIMA (never in mitosis gene a)- related kinase 6 ENST00000297142 NEUROD6 Neurogenic differentiation 6 ENST00000375724 NM_005384 NFIL3 Nuclear factor, interleukin 3 regulated ENST00000329043 NM_152995 NFXL1 Nuclear transcription factor, X- box binding-like 1 ENST00000265259 NIT2 Nitrilase family, member 2 ENST00000295886 NKX6-1 NK6 homeobox 1 ENST00000298087 NM_007363 NONO Non-POU domain containing, octamer-binding ENST00000367158 NM_015718 NOX3 NADPH oxidase 3 ENST00000361505 NP Nucleoside phosphorylase ENST00000378115 NP_001003702.1 ENST00000279907 NP_001006948.1 ENST00000370640 NP_001009997.1 ENST00000340967 NP_001010887.2 ENST00000335160 NP_001012735.1 ENST00000374884 NP_001012986.2 ENST00000344380 NP_001013646.1 ENST00000388936 NP_001013712.1 ENST00000378877 NP_001013726.1 ENST00000377957 NP_001019851.1 ENST00000374251 NP_001020436.1 ENST00000360388 NP_001025029.1 ENST00000021776 NP_001025037.1 ENST00000334306 NP_001025041.1 ENST00000343217 NP_001028747.1 ENST00000315313 NP_001028831.1 ENST00000332968 NP_001030177.1 ENST00000381078 NP_001034981.1 ENST00000382142 NP_001035536.1 ENST00000262498 NP_037374.1 ENST00000361462 NP_055906.2 ENST00000381240 NP_056174.1 ENST00000358677 NP_056350.1 ENST00000367220 NP_056368.1 ENST00000226105 NP_057576.2 ENST00000344442 NP_057732.1 ENST00000288168 NP_060028.2 ENST00000310452 NP_060222.2 ENST00000354544 NP_060325.3 ENST00000264434 NP_060350.1 ENST00000372543 NP_060485.3 ENST00000252100 NP_060972.3 ENST00000285871 NP_065930.2 ENST00000297788 NP_073579.2 ENST00000292199 NP_078894.2 ENST00000306049 NP_078959.2 ENST00000281924 NP_112185.1 ENST00000317568 NP_114110.1 ENST00000325106 NP_114162.1 ENST00000329713 NP_115622.2 ENST00000367003 NP_116094.2 ENST00000375706 NP_443121.1 ENST00000319194 NP_588616.1 ENST00000295488 NP_598375.1 ENST00000370922 NP_659404.2 ENST00000280571 NP_659495.1 ENST00000357613 NP_660297.1 ENST00000309733 NP_689613.1 ENST00000329620 NP_689826.1 ENST00000323352 NP_694553.1 ENST00000257034 NP_710163.1 ENST00000321510 NP_775908.1 ENST00000295723 NP_775919.2 ENST00000383671 NP_776160.1 ENST00000357872 NP_776161.2 ENST00000374900 NP_777572.1 ENST00000333598 NP_777578.1 ENST00000354310 NP_778223.1 ENST00000379190 NP_787068.2 ENST00000318586 NP_848650.2 ENST00000307201 NP_937790.1 ENST00000331738 NP_937992.1 ENST00000338588 NP_995327.1 ENST00000320866 NP_997283.1 ENST00000367553 NPL N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) ENST00000296930 NPM1 Nucleophosmin (nucleolar phosphoprotein B23, numatrin) ENST00000342694 NM_003995 NPR2 Natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B) ENST00000338566 NM_006174 NPY5R Neuropeptide Y receptor Y5 ENST00000290426 NPY6R Neuropeptide Y receptor Y6 (pseudogene) ENST00000374570 NR_003086.1 ENST00000374816 NM_001024628 NRP1 Neuropilin 1 NM_001024629 NM_003873 ENST00000355783 NM_022455 NSD1 Nuclear receptor binding SET NM_172349 domain protein 1 ENST00000293973 NM_006181 NTN2L Netrin 2-like (chicken) ENST00000361681 NU6M_HUMAN ENST00000309188 NM_024815.3 NUDT18 Nudix (nucleoside diphosphate linked moiety X)-type motif 18 ENST00000354226 NUP214 Nucleoporin 214 kDa ENST00000295119 NUP35 Nucleoporin 35 kDa ENST00000372788 NM_032946 NXF5 Nuclear RNA export factor 5 NM_033152 NM_033153 NM_033154 NM_033155 ENST00000357403 NM_022463 NXN Nucleoredoxin ENST00000368845 OAT Ornithine aminotransferase (gyrate atrophy) ENST00000371226 OMA1 OMA1 homolog, zinc metallopeptidase (S. cerevisiae) ENST00000304646 NM_012360 OR1F1 Olfactory receptor, family 1, subfamily F, member 1 ENST00000259357 NM_001004451 OR1J1 Olfactory receptor, family 1, subfamily J, member 1 ENST00000359776 NM_001005479 OR5H6 Olfactory receptor, family 5, subfamily H, member 6 ENST00000368144 NM_001005184 OR6K6 Olfactory receptor, family 6, subfamily K, member 6 ENST00000339258 NM_001005278 OR6N2 Olfactory receptor, family 6, subfamily N, member 2 ENST00000319481 OSBPL1A Oxysterol binding protein-like 1A ENST00000372858 PABPC4 Poly(A) binding protein, cytoplasmic 4 (inducible form) ENST00000366889 NM_001080378.1 PACRG PARK2 co-regulated NM_001080379.1 NM_152410 ENST00000375481 NM_007365 PADI2 Peptidyl arginine deiminase, type II ENST00000290507 NM_012387 PADI4 Peptidyl arginine deiminase, type IV ENST00000221265 NM_019088 PAF1 Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae) ENST00000376141 NM_007003 PAGE4 P antigen family, member 4 (prostate associated) ENST00000381543 NM_006451 PAIP1 Poly(A) binding protein NM_182789.2 interacting protein 1 NM_183323 ENST00000379568 NM_017906 PAK1IP1 PAK1 interacting protein 1 ENST00000370180 PALMD Palmdelphin ENST00000358107 NM_018109 PAPD1 PAP associated domain containing 1 ENST00000338639 PARK7 Parkinson disease (autosomal recessive, early onset) 7 ENST00000310366 PARP15 Poly (ADP-ribose) polymerase family, member 15 ENST00000377123 NM_006192 PAX1 Paired box 1 ENST00000368465 NM_020524 PBXIP1 Pre-B-cell leukemia homeobox interacting protein 1 ENST00000231173 NM_018935 PCDHB15 Protocadherin beta 15 ENST00000194155 NM_018936 PCDHB2 Protocadherin beta 2 ENST00000297529 NM_006197.3 PCM1 Pericentriolar material 1 ENST00000367384 NM_005389 PCMT1 Protein-L-isoaspartate (D- aspartate) O-methyltransferase ENST00000295992 NM_013363 PCOLCE2 Procollagen C-endopeptidase enhancer 2 ENST00000359062 NM_000921 PDE3A Phosphodiesterase 3A, cGMP- inhibited ENST00000358923 PDE4D Phosphodiesterase 4D, cAMP- specific (phosphodiesterase E3 dunce homolog, Drosophila) ENST00000266395 PDE6H Phosphodiesterase 6H, cGMP- specific, cone, gamma ENST00000354513 PDGFA Platelet-derived growth factor alpha polypeptide ENST00000329399 PDLIM1 PDZ and LIM domain 1 (elfin) ENST00000308354 NM_021630 PDLIM2 PDZ and LIM domain 2 NM_176871 (mystique) NM_198042 ENST00000369032 NM_020381 PDSS2 Prenyl (decaprenyl) diphosphate synthase, subunit 2 ENST00000344770 NM_002614 PDZK1 PDZ domain containing 1 ENST00000261313 PEBP1 Phosphatidylethanolamine binding protein 1 ENST00000263985 PET112L PET112-like (yeast) ENST00000225873 NM_000286 PEX12 Peroxisomal biogenesis factor 12 ENST00000367756 NM_000288 PEX7 Peroxisomal biogenesis factor 7 ENST00000374516 PHF1 PHD finger protein 1 ENST00000370800 NM_001015877 PHF6 PHD finger protein 6 NM_032335 NM_032458 ENST00000378659 NM_001037537.1 PHYH Phytanoyl-CoA 2-hydroxylase NM_006214 ENST00000367728 NM_002642 PIGC Phosphatidylinositol glycan NM_153747 anchor biosynthesis, class C ENST00000372689 NM_015937 PIGT Phosphatidylinositol glycan anchor biosynthesis, class T ENST00000374147 NM_017837 PIGV Phosphatidylinositol glycan anchor biosynthesis, class V ENST00000262039 PIK3C3 Phosphoinositide-3-kinase, class 3 ENST00000380994 PITRM1 Pitrilysin metallopeptidase 1 ENST00000361478 NM_001032396 PJA1 Praja 1 NM_022368 NM_145119 ENST00000262304 NM_000296.2 PKD1 Polycystic kidney disease 1 NM_001009944 (autosomal dominant) ENST00000372675 NM_013355 PKN3 Protein kinase N3 ENST00000367324 NM_000299 PKP1 Plakophilin 1 (ectodermal NM_001005337 dysplasia/skin fragility syndrome) ENST00000367466 NM_024420 PLA2G4A Phospholipase A2, group IVA (cytosolic, calcium-dependent) ENST00000216446 PLEK2 Pleckstrin 2 ENST00000341590 NM_006832 PLEKHC1 Pleckstrin homology domain containing, family C (with FERM domain) member 1 ENST00000361349 NM_001042663.1 PLEKHG5 Pleckstrin homology domain NM_001042664.1 containing, family G (with NM_001042665.1 RhoGef domain) member 5 NM_020631 NM_198681.2 ENST00000223127 NM_001084 PLOD3 Procollagen-lysine, 2- oxoglutarate 5-dioxygenase 3 ENST00000252590 NM_031310 PLVAP Plasmalemma vesicle associated protein ENST00000277585 NM_032812 PLXDC2 Plexin domain containing 2 ENST00000368276 PMF1 Polyamine-modulated factor 1 ENST00000342075 PMS1 PMS1 postmeiotic segregation increased 1 (S. cerevisiae) ENST00000388753 PO210_HUMAN ENST00000382229 POK9_HUMAN ENST00000215960 POLR2F Polymerase (RNA) II (DNA directed) polypeptide F ENST00000275569 POMZP3 POM (POM121 homolog, rat) and ZP3 fusion ENST00000379747 NM_006475 POSTN Periostin, osteoblast specific factor ENST00000344265 NM_000306 POU1F1 POU class 1 homeobox 1 ENST00000373232 PPA1 Pyrophosphatase (inorganic) 1 ENST00000372561 NM_001080850 PPCS Phosphopantothenoylcysteine synthetase ENST00000319610 NM_006240 PPEF1 Protein phosphatase, EF-hand NM_152226.1 calcium binding domain 1 ENST00000372341 NM_005729 PPIF Peptidylprolyl isomerase F (cyclophilin F) ENST00000253329 NM_139126 PPIL4 Peptidylprolyl isomerase (cyclophilin)-like 4 ENST00000357726 PRA12_HUMAN ENST00000389488 PRIM2A ENST00000287878 PRKAG2 Protein kinase, AMP-activated, gamma 2 non-catalytic subunit ENST00000379066 PRKD3 Protein kinase D3 ENST00000234071 NM_000312 PROC Protein C (inactivator of coagulation factors Va and VIIIa) ENST00000257860 NM_006262 PRPH Peripherin ENST00000161006 NM_022119 PRSS22 Protease, serine, 22 ENST00000284885 NM_002772 PRSS7 Protease, serine, 7 (enterokinase) ENST00000376588 NM_021154 PSAT1 Phosphoserine NM_058179 aminotransferase 1 ENST00000342601 PSIP1 PC4 and SFRS1 interacting protein 1 ENST00000261479 PSMA6 Proteasome (prosome, macropain) subunit, alpha type, 6 ENST00000275605 PSPH Phosphoserine phosphatase ENST00000331920 PTCH ENST00000372192 NM_003738 PTCH2 Patched homolog 2 (Drosophila) ENST00000370758 NM_000959 PTGFR Prostaglandin F receptor (FP) NM_001039585 ENST00000263708 PTPN4 Protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte) ENST00000367364 NM_002838 PTPRC Protein tyrosine phosphatase, NM_080921 receptor type, C NM_080922 NM_080923.2 ENST00000295927 NM_002852 PTX3 Pentraxin-related gene, rapidly induced by IL-1 beta ENST00000373742 NM_001020658.1 PUM1 Pumilio homolog 1 (Drosophila) NM_014676 ENST00000216200 NM_002854 PVALB Parvalbumin ENST00000376902 Q16653-5 ENST00000371277 Q4TT42_HUMAN ENST00000377439 Q4V339_HUMAN ENST00000316733 Q5SWJ0_HUMAN ENST00000331562 Q5T6X4_HUMAN ENST00000371932 Q5VXJ0_HUMAN ENST00000320930 Q68DA7_HUMAN ENST00000359049 Q6AI40_HUMAN ENST00000340357 Q6NXN4_HUMAN ENST00000359425 Q6ZNB4_HUMAN ENST00000327804 Q6ZSN3_HUMAN ENST00000376812 Q6ZSR2_HUMAN ENST00000377722 Q6ZVM9_HUMAN ENST00000359074 Q7Z4R2_HUMAN ENST00000333898 Q86TS2_HUMAN ENST00000335624 Q86VR7_HUMAN ENST00000280876 Q8IXV1_HUMAN ENST00000341249 Q8N712_HUMAN ENST00000327979 Q8NF41_HUMAN ENST00000328798 Q8NI66_HUMAN ENST00000358148 Q8TEB0_HUMAN ENST00000254579 Q8TEE6_HUMAN ENST00000329244 Q96S36_HUMAN ENST00000272845 Q96SS0_HUMAN ENST00000343811 Q9H579-2 ENST00000382764 Q9H606_HUMAN ENST00000314272 Q9NT86_HUMAN ENST00000356397 Q9P1D0_HUMAN ENST00000380195 Q9Y6V0-3 ENST00000382282 QDPR Quinoid dihydropteridine reductase ENST00000367495 RAB32 RAB32, member RAS oncogene family ENST00000264158 RAB3GAP1 RAB3 GTPase activating protein subunit 1 (catalytic) ENST00000337311 NM_001024647.2 RAB3IP RAB3A interacting protein NM_022456 (rabin3) NM_175623 NM_175624 NM_175625.2 ENST00000251507 RABGAP1L RAB GTPase activating protein 1-like ENST00000251849 NM_002880 RAF1 V-raf-1 murine leukemia viral oncogene homolog 1 ENST00000389591 NM_002271 RANBP5 RAN binding protein 5 ENST00000383772 RARB_HUMAN ENST00000369523 RARSL ENST00000222145 NM_017805 RASIP1 Ras interacting protein 1 ENST00000319715 NM_006910 RBBP6 Retinoblastoma binding protein 6 NM_018703 ENST00000315658 RBED1 RNA binding motif and ELMO/CED-12 domain 1 ENST00000254105 NM_005105 RBM8A RNA binding motif protein 8A ENST00000378415 NM_001268 RCBTB2 Regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 2 ENST00000265881 REXO2 REX2, RNA exonuclease 2 homolog (S. cerevisiae) ENST00000367669 NM_001001740.2 RFWD2 Ring finger and WD repeat NM_022457 domain 2 ENST00000372092 RGR Retinal G protein coupled receptor ENST00000367460 NM_130782 RGS18 Regulator of G-protein signaling 18 ENST00000371175 NM_000324 RHAG Rh-associated glycoprotein ENST00000378013 RHG26_HUMAN ENST00000303700 RHOH Ras homolog gene family, member H ENST00000257700 NM_021930 RINT1 RAD50 interactor 1 ENST00000296277 RL39L_HUMAN ENST00000311413 NM_032015 RNF26 Ring finger protein 26 ENST00000263808 NM_002944 ROS1 V-ros UR2 sarcoma virus oncogene homolog 1 (avian) ENST00000381209 RPAIN RPA interacting protein ENST00000359429 NM_006916.1 RPE Ribulose-5-phosphate-3- NM_199229 epimerase ENST00000361575 NM_001000 RPL39 Ribosomal protein L39 ENST00000315741 RPL5 Ribosomal protein L5 ENST00000378203 NM_001097590.1 RPP38 Ribonuclease P/MRP 38 kDa NM_006414 subunit NM_183005 ENST00000341844 RPS12 Ribosomal protein S12 ENST00000359364 RPS4X Ribosomal protein S4, X-linked ENST00000358328 NM_031464 RPS6KL1 Ribosomal protein S6 kinase- like 1 ENST00000246792 RRAS Related RAS viral (r-ras) oncogene homolog ENST00000260563 RTCD1 RNA terminal phosphate cyclase domain 1 ENST00000312295 NM_153708 RTP1 Receptor (chemosensory) transporter protein 1 ENST00000369724 RWDD2 ENST00000368738 NM_002965 S100A9 S100 calcium binding protein A9 ENST00000296370 S100P S100 calcium binding protein P ENST00000359674 S6A12_HUMAN ENST00000335556 NM_182610 SAMD7 Sterile alpha motif domain containing 7 ENST00000367469 NM_015278 SASH1 SAM and SH3 domain containing 1 ENST00000379253 SAT ENST00000341787 SBSN Suprabasin ENST00000255390 NM_004589 SCO1 SCO cytochrome oxidase deficient homolog 1 (yeast) ENST00000371514 NM_001007098.1 SCP2 Sterol carrier protein 2 NM_001007099.1 NM_001007100.1 NM_001007250 NM_002979 ENST00000327872 SDHA Succinate dehydrogenase complex, subunit A, flavoprotein (Fp) ENST00000236147 NM_000655.3 SELL Selectin L (lymphocyte adhesion molecule 1) ENST00000379122 NM_020210.3 SEMA4B Sema domain, immunoglobulin NM_198925.2 domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4B ENST00000357877 NM_004263 SEMA4F Sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4F ENST00000340912 NM_145204 SENP8 SUMO/sentrin specific peptidase family member 8 ENST00000341584 SERPINA6 Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6 ENST00000258405 SERPINE2 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 ENST00000295777 NM_005025 SERPINI1 Serpin peptidase inhibitor, clade I (neuroserpin), member 1 ENST00000264677 NM_006217 SERPINI2 Serpin peptidase inhibitor, clade I (pancpin), member 2 ENST00000335508 NM_001005526.1 SF3B1 Splicing factor 3b, subunit 1, NM_012433 155 kDa ENST00000330854 SFR14_HUMAN ENST00000376280 SFRS1 Splicing factor, arginine/serine- rich 1 (splicing factor 2, alternate splicing factor) ENST00000334121 NM_001077199.1 SFRS12 Splicing factor, arginine/serine- NM_139168 rich 12 ENST00000370201 SFXN3 Sideroflexin 3 ENST00000263753 NM_001012409.1 SGOL1 Shugoshin-like 1 (S. pombe) NM_001012410 NM_001012413.1 NM_138484 ENST00000379698 NM_001024666 SH3KBP1 SH3-domain kinase binding NM_031892 protein 1 ENST00000316341 NM_005072 SLC12A4 Solute carrier family 12 (potassium/chloride transporters), member 4 ENST00000321925 SLC14A1 Solute carrier family 14 (urea transporter), member 1 (Kidd blood group) ENST00000376494 NM_005073 SLC15A1 Solute carrier family 15 (oligopeptide transporter), member 1 ENST00000345033 NM_003058 SLC22A2 Solute carrier family 22 (organic cation transporter), member 2 ENST00000263255 SLC25A17 Solute carrier family 25 (mitochondrial carrier; peroxisomal membrane protein, 34 kDa), member 17 ENST00000338602 NM_004213 SLC28A1 Solute carrier family 28 NM_201651 (sodium-coupled nucleoside transporter), member 1 ENST00000335244 NM_181776 SLC36A2 Solute carrier family 36 (proton/amino acid symporter), member 2 ENST00000367714 SLC9A11 Solute carrier family 9, member 11 ENST00000350148 NM_005905 SMAD9 SMAD family member 9 ENST00000358026 NM_003072 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 ENST00000283131 NM_003601 SMARCA5 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5 ENST00000374785 SMC2L1 ENST00000379494 SMPX Small muscle protein, X-linked ENST00000308624 NM_018968.2 SNTG2 Syntrophin, gamma 2 ENST00000368982 SNX3 Sorting nexin 3 ENST00000371227 SORBS1 Sorbin and SH3 domain containing 1 ENST00000340356 NM_018419 SOX18 SRY (sex determining region Y)-box 18 ENST00000227135 SPA17 Sperm autoantigenic protein 17 ENST00000357804 NM_003971 SPAG9 Sperm associated antigen 9 ENST00000280191 SPATA4 Spermatogenesis associated 4 ENST00000372659 NM_020398 SPINLW1 Serine peptidase inhibitor-like, NM_080827 with Kunitz and WAP domains 1 NM_181502 (eppin) ENST00000371258 NM_012444 SPO11 SPO11 meiotic protein NM_198265 covalently bound to DSB homolog (S. cerevisiae) ENST00000237623 SPP1 Secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) ENST00000307122 NM_005987 SPRR1A Small proline-rich protein 1A ENST00000244891 NM_032681 SPRYD5 SPRY domain containing 5 ENST00000372739 NM_003127 SPTAN1 Spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) ENST00000262554 SPTLC1 Serine palmitoyltransferase, long chain base subunit 1 ENST00000382562 NM_001047 SRD5A1 Steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4- dehydrogenase alpha 1) ENST00000336613 NM_182691 SRPK2 SFRS protein kinase 2 NM_182692 ENST00000371320 NM_001009955 SSBP3 Single stranded DNA binding NM_018070 protein 3 NM_145716 ENST00000320370 SSFA2 Sperm specific antigen 2 ENST00000278412 NM_003146 SSRP1 Structure specific recognition protein 1 ENST00000337768 ST65G_HUMAN ENST00000225276 ST6GALNAC2 ST6 (alpha-N-acetyl- neuraminyl-2,3-beta-galactosyl- 1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 ENST00000388888 NM_017564 STAB2 Stabilin 2 ENST00000380854 NM_003155 STC1 Stanniocalcin 1 ENST00000375333 NM_004197 STK19 Serine/threonine kinase 19 NM_032454 ENST00000376541 NM_001032296 STK24 Serine/threonine kinase 24 NM_003576 (STE20 homolog, yeast) ENST00000378577 STOML2 Stomatin (EPB72)-like 2 ENST00000267540 STON2 Stonin 2 ENST00000222812 NM_004603 STX1A Syntaxin 1A (brain) ENST00000273666 NM_014980.1 STXBP5L Syntaxin binding protein 5-like ENST00000378631 NM_003850 SUCLA2 Succinate-CoA ligase, ADP- forming, beta subunit ENST00000369899 NM_016169 SUFU Suppressor of fused homolog (Drosophila) ENST00000377973 SUGT1 SGT1, suppressor of G2 allele of SKP1 (S. cerevisiae) ENST00000371001 NM_014258 SYCP2 Synaptonemal complex protein 2 ENST00000376303 SYPH_HUMAN ENST00000334568 NM_001077503.1 TAC4 Tachykinin 4 (hemokinin) NM_001077504.1 NM_001077505.1 NM_001077506.1 NM_170685.2 ENST00000357300 TAF12 TAF12 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 20 kDa ENST00000337256 NM_005681 TAF1A TATA box binding protein NM_139352 (TBP)-associated factor, RNA polymerase I, A, 48 kDa ENST00000344095 NM_005641 TAF6 TAF6 RNA polymerase II, TATA NM_139122.1 box binding protein (TBP)- NM_139123.1 associated factor, 80 kDa NM_139315 ENST00000374699 TAL2 T-cell acute lymphocytic leukemia 2 ENST00000259075 TANK_HUMAN ENST00000355975 NM_017714 TASP1 Taspase, threonine aspartase, 1 ENST00000265393 NM_001079864.1 TAX1BP1 Tax1 (human T-cell leukemia NM_006024 virus type I) binding protein 1 ENST00000380377 TBCA Tubulin folding cofactor A ENST00000373296 NM_016954 TBX22 T-box 22 ENST00000372680 TCAL5_HUMAN ENST00000372671 TCEAL7 Transcription elongation factor A (SII)-like 7 ENST00000369397 TCF7L2 Transcription factor 7-like 2 (T- cell specific, HMG-box) ENST00000286956 NM_153046 TDRD9 Tudor domain containing 9 ENST00000265993 TECT3_HUMAN ENST00000239462 TENN_HUMAN ENST00000374896 NM_001032281 TFPI Tissue factor pathway inhibitor NM_006287 (lipoprotein-associated coagulation inhibitor) ENST00000305126 TGFBI Transforming growth factor, beta-induced, 68 kDa ENST00000212355 NM_003243 TGFBR3 Transforming growth factor, beta receptor III ENST00000296736 NM_030953 TIGD6 Tigger transposable element derived 6 ENST00000296802 TIP1_HUMAN ENST00000279992 TIRAP_HUMAN ENST00000265284 TLE4_HUMAN ENST00000389469 TLN2 Talin 2 ENST00000260010 TLR2 Toll-like receptor 2 ENST00000370196 TLX1_HUMAN ENST00000261789 NM_001014842.1 TM9SF1 Transmembrane 9 superfamily NM_006405 member 1 ENST00000245361 NM_004800 TM9SF2 Transmembrane 9 superfamily member 2 ENST00000288025 NM_144676 TMED6 Transmembrane emp24 protein transport domain containing 6 ENST00000368671 TMEM12 ENST00000379828 NM_198507 TMEM157 Transmembrane protein 157 ENST00000292246 NM_018075 TMEM16K Transmembrane protein 16K ENST00000353948 TMEM20 Transmembrane protein 20 ENST00000383743 TMEM42 Transmembrane protein 42 ENST00000381964 NM_006134 TMEM50B Transmembrane protein 50B ENST00000310991 NM_178545 TMEM52 Transmembrane protein 52 ENST00000356838 NM_144649 TMEM71 Transmembrane protein 71 ENST00000264331 NM_001068.2 TOP2B Topoisomerase (DNA) II beta 180 kDa ENST00000329305 TPM2 Tropomyosin 2 (beta) ENST00000367471 NM_003292.2 TPR Translocated promoter region (to activated MET oncogene) ENST00000357819 NM_001011658.1 TRAPPC2 Trafficking protein particle NM_014563.3 complex 2 ENST00000373162 TRAPPC3 Trafficking protein particle complex 3 ENST00000297221 TRERF1 Transcriptional regulating factor 1 ENST00000336708 TRIM16 Tripartite motif-containing 16 ENST00000225583 TRIM16L Tripartite motif-containing 16- like ENST00000376674 NM_003449 TRIM26 Tripartite motif-containing 26 ENST00000272395 NM_138800 TRIM43 Tripartite motif-containing 43 ENST00000353317 NM_033058 TRIM55 Tripartite motif-containing 55 NM_184085 NM_184086 NM_184087 ENST00000251607 NM_182916 TRNT1 TRNA nucleotidyl transferase, CCA-adding, 1 ENST00000375041 NM_001039705.1 TRO Trophinin NM_016157.2 NM_177556.1 ENST00000379645 NM_003305 TRPC3 Transient receptor potential cation channel, subfamily C, member 3 ENST00000312449 NM_017662 TRPM6 Transient receptor potential cation channel, subfamily M, member 6 ENST00000339687 TRYA1_HUMAN ENST00000361875 NM_014779 TSC22D2 TSC22 domain family, member 2 ENST00000355053 NM_025244 TSGA10 Testis specific, 10 NM_182911 ENST00000322038 NM_005786 TSHZ1 Teashirt zinc finger homeobox 1 ENST00000381121 TSN32_HUMAN ENST00000377711 NM_145003 TSNARE1 T-SNARE domain containing 1 ENST00000315170 TSP50_HUMAN ENST00000372003 NM_005727 TSPAN1 Tetraspanin 1 ENST00000360913 NM_032037 TSSK6 Testis-specific serine kinase 6 ENST00000382320 NM_001007795 TTC6 Tetratricopeptide repeat domain 6 ENST00000369798 NM_003318 TTK TTK protein kinase ENST00000242261 NM_000474 TWIST1 Twist homolog 1 (acrocephalosyndactyly 3; Saethre-Chotzen syndrome) (Drosophila) ENST00000380122 TXLNG_HUMAN ENST00000217515 TXNL1 Thioredoxin-like 1 ENST00000271469 NM_003115 UAP1 UDP-N-acteylglucosamine pyrophosphorylase 1 ENST00000222402 UBE2D4 Ubiquitin-conjugating enzyme E2D 4 (putative) ENST00000272930 UBE2F ENST00000371077 NM_152489 UBE2U Ubiquitin-conjugating enzyme E2U (putative) ENST00000232165 NM_000462.2 UBE3A Ubiquitin protein ligase E3A NM_130838 (human papilloma virus E6- NM_130839.1 associated protein, Angelman syndrome) ENST00000252108 NM_004788 UBE4A Ubiquitination factor E4A (UFD2 homolog, yeast) ENST00000343638 NM_001076683.1 UBTF Upstream binding transcription NM_001076684.1 factor, RNA polymerase I NM_014233 ENST00000265616 NM_005671.2 UBXD6 UBX domain containing 6 ENST00000337130 UGP2 UDP-glucose pyrophosphorylase 2 ENST00000305107 NM_021139.2 UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4 ENST00000282507 NM_174914 UGT3A2 UDP glycosyltransferase 3 family, polypeptide A2 ENST00000257548 NM_032663 USP30 Ubiquitin specific peptidase 30 ENST00000258499 NM_001042403.1 USP44 Ubiquitin specific peptidase 44 NM_032147 ENST00000286428 NM_003372 VBP1 Von Hippel-Lindau binding protein 1 ENST00000251127 VGCNL1 ENST00000372207 VMD2L2 ENST00000355155 VP13B_HUMAN ENST00000300793 NM_021729.4 VPS11 Vacuolar protein sorting 11 homolog (S. cerevisiae) ENST00000354367 NM_018668 VPS33B Vacuolar protein sorting 33 homolog B (yeast) ENST00000381313 NM_003385 VSNL1 Visinin-like 1 ENST00000369277 NM_198496 VWA2 Von Willebrand factor A domain containing 2 ENST00000368938 NM_001024934 WASF1 WAS protein family, member 1 NM_001024935 NM_001024936 NM_003931 ENST00000299764 NM_153210.3 WDR16 WD repeat domain 16 ENST00000369965 NM_014969 WDR47 WD repeat domain 47 ENST00000262144 NM_030581 WDR59 WD repeat domain 59 ENST00000287380 NM_145647 WDR67 WD repeat domain 67 ENST00000278856 WDR74 WD repeat domain 74 ENST00000289953 NM_130896 WFDC8 WAP four-disulfide core domain 8 NM_181510 ENST00000265293 NM_015238 WWC1 WW and C2 domain containing 1 ENST00000297303 NM_173683 XKR6 XK, Kell blood group complex subunit-related family, member 6 ENST00000340777 XP_498354.2 ENST00000351427 XP_931530.1 ENST00000274299 XP_932027.1 ENST00000342036 XP_932444.1 ENST00000361410 XP_942995.1 ENST00000306716 XP_944511.1 ENST00000375128 XPA Xeroderma pigmentosum, complementation group A ENST00000311755 XR_000659.1 ENST00000262887 XRCC1 X-ray repair complementing defective repair in Chinese hamster cells 1 ENST00000325680 YLPM1_HUMAN ENST00000261749 ZA20D3 ENST00000373515 ZBTB8_HUMAN ENST00000375947 ZCCHC6 Zinc finger, CCHC domain containing 6 ENST00000359775 ZDH14_HUMAN ENST00000341191 ZF36_HUMAN ENST00000370609 NM_003413 ZIC3 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila) ENST00000381591 NM_006624 ZMYND11 Zinc finger, MYND domain NM_212479 containing 11 ENST00000298585 NM_138462 ZMYND19 Zinc finger, MYND-type containing 19 ENST00000355114 ZN565_HUMAN ENST00000299871 ZNF211 Zinc finger protein 211 ENST00000263095 NM_003417 ZNF264 Zinc finger protein 264 ENST00000262990 NM_014487 ZNF330 Zinc finger protein 330 ENST00000335815 NM_005649 ZNF354A Zinc finger protein 354A ENST00000221315 NM_014650 ZNF432 Zinc finger protein 432 NM_025040 ENST00000372524 NM_032772 ZNF503 Zinc finger protein 503 ENST00000291598 NM_152478 ZNF583 Zinc finger protein 583 ENST00000248125 ZNF598 Zinc finger protein 598 ENST00000379365 NM_152577 ZNF645 Zinc finger protein 645 ENST00000357130 NM_024733.3 ZNF665 Zinc finger protein 665 ENST00000372503 ZNF691 Zinc finger protein 691 ENST00000295131 NM_182521 ZSWIM2 Zinc finger, SWIM-type containing 2

TABLE 5 miR-489 targets identified by miRanda and L2L Target Gene Accession No: Gene Name AHSG NM_001622.2 alpha-2-HS-glycoprotein GI: 156523969 AMELY NM_001143.1 amelogenin, Y-linked GI: 4502072 BMP7 NM_001719.1 bone morphogenetic protein 7 GI: 4502426 (osteogenic protein 1) CDH11 NM_001797.2 cadherin 11, type 2, OB-cadherin GI: 16306531 (osteoblast) CHRD NM_003741.2 chordin GI: 30089979 CHRDL2 NM_015424.3 chordin-like 2 GI: 40353768 EN1 NM_001426.3 engrailed homeobox 1 GI: 126090908 MAPK8 NM_002750.2 mitogen-activated protein kinase 8 GI: 20986493 MAPK8 NM_139046.1 mitogen-activated protein kinase 8 GI: 20986518 MAPK8 NM_139047.1 mitogen-activated protein kinase 8 GI: 20986520 MAPK8 NM_139049.1 mitogen-activated protein kinase 8 GI: 20986522 MGP NM_000900.2 matrix Gla protein GI: 49574513 PAX1 NM_006192.3 paired box gene 1 GI: 153791841 PEX7 NM_000288.1 peroxisomal biogenesis factor 7 GI: 4505730 POSTN NM_006475.1 periostin, osteoblast specific factor GI: 5453833 SPP1 NM_001040058.1 secreted phosphoprotein 1 GI: 91206461 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) SPP1 NM_000582.2 secreted phosphoprotein 1 GI: 38146097 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) SPP1 NM_001040060.1 secreted phosphoprotein 1 GI: 91598938 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) SUFU NM_016169.2 suppressor of fused homolog GI: 19923478 (Drosophila) TRAPPC2 NM_001011658.1 trafficking protein particle complex 2 GI: 58533178 TRAPPC2 NM_014563.3 trafficking protein particle complex 2 GI: 58533177 TWIST1 NM_000474.3 twist homolog 1 (acrocephalosyndactyly GI: 68160957 3; Saethre-Chotzen syndrome) (Drosophila)

TABLE 6 All Targets of miR-148b RefSeq Transcript ID. Accession No. Target Name Gene ENSG00000008311 NM_005763 AASS Aminoadipate-semialdehyde synthase ABCB7 ATP-binding cassette, sub- family B (MDR/TAP), member 7 ENSG00000108846 NM_003786 ABCC3 ATP-binding cassette, sub- family C (CFTR/MRP), member 3 ENSG00000117528 NM_002858 ABCD3 ATP-binding cassette, sub- family D (ALD), member 3 ENSG00000100997 NM_001042472.1 ABHD12 Abhydrolase domain NM_015600 containing 12 ENSG00000112077 NM_000324 ABI1 Abl-interactor 1 ENSG00000136754 NM_001012750 NM_001012751 NM_001012752 NM_005470 ENSG00000108798 NM_016428 ABI3 ABI gene family, member 3 ENSG00000167315 NM_006111 ACAA2 Acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl- Coenzyme A thiolase) ENSG00000135847 NM_032360 ACBD6 Acyl-Coenzyme A binding domain containing 6 ENSG00000101473 NM_005469 ACOT8 Acyl-CoA thioesterase 8 NM_183385 NM_183386 ENSG00000102575 NM_001611 ACP5 Acid phosphatase 5, tartrate resistant ENSG00000187003 NM_006687 ACTL7A Actin-like 7A ENSG00000163485 NM_000674 ADORA1 Adenosine A1 receptor NM_001048230.1 ENSG00000150594 NM_000681 ADRA2A Adrenergic, alpha-2A-, receptor ENSG00000106688 NM_004170 AFG3L2 AFG3 ATPase family gene 3- ENSG00000141385 NM_006796 like 2 (yeast) ENSG00000166748 NM_152336.2 AGBL1 ATP/GTP binding protein-like 1 ENSG00000165923 NM_024783 AGBL2 ATP/GTP binding protein-like 2 ENSG00000144891 NM_000685 AGTR1 Angiotensin II receptor, type 1 NM_004835 NM_009585 NM_031850 NM_032049 ENSG00000134817 NM_005161 AGTRL1 Angiotensin II receptor-like 1 ENSG00000004455 NM_001625 AK2 Adenylate kinase 2 NM_013411 AK3L2 ENSG00000121057 NM_003488 AKAP1 A kinase (PRKA) anchor ENSG00000204689 protein 1 ENSG00000206519 ENSG00000117020 NM_005465 AKT3 V-akt murine thymoma viral NM_181690 oncogene homolog 3 (protein kinase B, gamma) ENSG00000155749 NM_139163 ALS2CR12 Amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 12 ENSG00000082146 NM_018571 ALS2CR2 Amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 AMZ2_HUMAN ENSG00000176248 NM_013366 ANAPC2 Anaphase promoting complex subunit 2 ENSG00000091879 NM_001147 ANGPT2 Angiopoietin 2 ANKRD10 Ankyrin repeat domain 10 ENSG00000133302 NM_032290 ANKRD32 Ankyrin repeat domain 32 ENSG00000168096 NM_133450 ANKS3 Ankyrin repeat and sterile alpha motif domain containing 3 ENSG00000163516 NM_001042410.1 ANKZF1 Ankyrin repeat and zinc finger NM_018089.2 domain containing 1 ENSG00000213983 NM_003917 AP1G2 Adaptor-related protein NM_080545 complex 1, gamma 2 subunit ENSG00000157823 NM_005829 AP3S2 Adaptor-related protein complex 3, sigma 2 subunit ENSG00000204305 NM_001136 APBA1 Amyloid beta (A4) precursor ENSG00000206253 NM_172197 protein-binding, family A, ENSG00000206320 member 1 (X11) ENSG00000166313 NM_001164.2 APBB1 Amyloid beta (A4) precursor NM_145689 protein-binding, family B, member 1 (Fe65) ENSG00000110244 NM_000482 APOA4 Apolipoprotein A-IV ENSG00000111701 NM_001644 APOBEC1 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 ENSG00000204444 NM_019101 APOM Apolipoprotein M ENSG00000206304 ENSG00000206409 ENSG00000178301 NM_173039 AQP11 Aquaporin 11 ENSG00000165269 NM_001170 AQP7 Aquaporin 7 ENSG00000105127 NM_005858 ARF4 ADP-ribosylation factor 4 ENSG00000168374 NM_001660 ENSG00000066777 NM_006421 ARFGEF1 ADP-ribosylation factor guanine nucleotide-exchange factor 1(brefeldin A-inhibited) ENSG00000170540 NM_015161 ARL6IP1 ADP-ribosylation factor-like 6 interacting protein 1 ENSG00000140691 NM_024742.1 ARMC5 Armadillo repeat containing 5 ENSG00000133794 NM_001030272 ARNTL Aryl hydrocarbon receptor ENSG00000159423 NM_001030273.1 nuclear translocator-like NM_001178 NM_003748 NM_170726 ARPC4 Actin related protein 2/3 complex, subunit 4, 20 kDa ENSG00000136950 NM_030978 ARPC5L Actin related protein 2/3 complex, subunit 5-like ENSG00000157399 NM_000047 ARSE Arylsulfatase E (chondrodysplasia punctata 1) ENSG00000141337 NM_014960 ARSG Arylsulfatase G ENSG00000156219 NM_001179 ART3 ADP-ribosyltransferase 3 ENSG00000119778 NM_017552.1 ATAD2B ATPase family, AAA domain containing 2B ENSG00000107669 NM_001001976 ATE1 Arginyltransferase 1 ENSG00000153147 NM_007041 NM_003601 ENSG00000125703 NM_032852 ATG4C ATG4 autophagy related 4 NM_178221 homolog C (S. cerevisiae) ENSG00000130734 NM_032885 ATG4D ATG4 autophagy related 4 homolog D (S. cerevisiae) ENSG00000198925 NM_001077198.1 ATG9A ATG9 autophagy related 9 NM_024085.3 homolog A (S. cerevisiae) ENSG00000101280 NM_015985 ATP2A1 ATPase, Ca++ transporting, ENSG00000196296 NM_004320.3 cardiac muscle, fast twitch 1 NM_173201 ATP2A2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 ENSG00000186009 NM_000705 ATP4B ATPase, H+/K+ exchanging, beta polypeptide ENSG00000182220 NM_005765 ATP6AP2 ATPase, H+ transporting, lysosomal accessory protein 2 ENSG00000159720 NM_004691 ATP6V0D1 ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d1 ATP6V1E2 ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E2 ENSG00000105193 NM_001020 ATP8A1 ATPase, aminophospholipid transporter (APLT), class I, type 8A, member 1 ENSG00000171953 NM_145691 ATPAF2 ATP synthase mitochondrial F1 complex assembly factor 2 ENSG00000149541 NM_012200 B3GAT3 Beta-1,3- glucuronyltransferase 3 (glucuronosyltransferase I) ENSG00000118276 NM_004775 B4GALT6 UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 6 ENSG00000081014 NM_007347 BAG1 BCL2-associated athanogene ENSG00000106588 NM_002787 BAG3 BCL2-associated athanogene 3 ENSG00000206580 NM_004722 BAGE B melanoma antigen ENSG00000135298 NM_001704 BAI3 Brain-specific angiogenesis inhibitor 3 BAIAP2 BAI1-associated protein 2 ENSG00000011132 NM_004886 BARD1 BRCA1 associated RING ENSG00000138376 NM_000465 domain 1 ENSG00000105327 NM_014417 BBC3 BCL2 binding component 3 BBS1 Bardet-Biedl syndrome 1 ENSG00000138686 NM_018190.2 BBS7 Bardet-Biedl syndrome 7 NM_176824 ENSG00000153094 NM_006538.3 BCL2L11 BCL2-like 11 (apoptosis NM_138621 facilitator) NM_138623 NM_207002 ENSG00000121380 NM_030766 BCL2L14 BCL2-like 14 (apoptosis NM_138722 facilitator) NM_138723 NM_138724 ENSG00000099385 NM_004765 BCL7C B-cell CLL/lymphoma 7C ENSG00000100739 NM_000710 BDKRB1 Bradykinin receptor B1 ENSG00000117133 NM_025065 BXDC5 Brix domain containing 5 C10orf130 ENSG00000165669 NM_022063 C10orf84 Chromosome 10 open reading frame 84 ENSG00000204856 NM_013300 C12orf24 Chromosome 12 open reading frame 24 ENSG00000180116 NM_001031748.2 C12orf40 Chromosome 12 open reading frame 40 ENSG00000179088 NM_001099336.1 C12orf42 Chromosome 12 open NM_198521.2 reading frame 42 ENSG00000153495 NM_152324 C13orf16 Chromosome 13 open reading frame 16 ENSG00000050130 NM_001098625.1 C14orf100 Chromosome 14 open NM_016475.3 reading frame 100 ENSG00000165555 NM_138791 C14orf148 Chromosome 14 open reading frame 148 ENSG00000108671 NM_002815 C14orf2 Chromosome 14 open reading frame 2 C14orf37 Chromosome 14 open reading frame 37 C14orf8 ENSG00000166920 NM_032413 C15orf48 Chromosome 15 open NM_197955 reading frame 48 ENSG00000125149 NM_025187 C16orf70 Chromosome 16 open reading frame 70 ENSG00000070761 NM_013242 C16orf80 Chromosome 16 open reading frame 80 ENSG00000101546 NM_024805 C18orf22 Chromosome 18 open reading frame 22 C18orf8 ENSG00000181392 NM_001039876.1 C19orf46 Chromosome 19 open NM_032878 reading frame 46 ENSG00000104979 NM_014047 C19orf53 Chromosome 19 open reading frame 53 ENSG00000106392 NM_020156 C1GALT1 Core 1 synthase, glycoprotein-N- acetylgalactosamine 3-beta- galactosyltransferase, 1 ENSG00000162384 NM_017887 C1orf123 Chromosome 1 open reading frame 123 ENSG00000160767 NM_006589 C1orf2 Chromosome 1 open reading NM_198264 frame 2 C1orf68 Chromosome 1 open reading frame 68 ENSG00000153363 NM_032705.3 C1orf97 Chromosome 1 open reading frame 97 ENSG00000165985 NM_001010908 C1QL3 Complement component 1, q subcomponent-like 3 ENSG00000213192 NM_015645 C1QTNF5 C1q and tumor necrosis factor related protein 5 ENSG00000133466 NM_031910 C1QTNF6 C1q and tumor necrosis NM_182486 factor related protein 6 ENSG00000186312 CA5BL Carbonic anhydrase VB-like ENSG00000157782 NM_001033677 CABP1 Calcium binding protein 1 NM_004276 NM_031205 ENSG00000153956 NM_000722 CACNA2D1 Calcium channel, voltage- dependent, alpha 2/delta subunit 1 ENSG00000169136 NM_012068 CAD Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase ENSG00000092529 NM_000070.2 CAPN3 Calpain 3, (p94) NM_024344 NM_173087 NM_173088.1 NM_173089 NM_173090 NM_212464.2 NM_212465.2 NM_212467.2 ENSG00000180881 NM_032606 CAPS2 Calcyphosine 2 ENSG00000187796 NM_052813 CARD9 Caspase recruitment domain family, member 9 ENSG00000153113 NM_001042440.1 CAST Calpastatin NM_001042441.1 NM_001042442.1 NM_001042443.1 NM_001042444.1 NM_001042445.1 NM_001042446.1 NM_001750.5 NM_173060 NM_173061 NM_173063.1 ENSG00000175294 NM_053054 CATSPER1 Cation channel, sperm associated 1 ENSG00000100211 NM_001002880 CBY1 Chibby homolog 1 NM_015373 (Drosophila) ENSG00000004766 NM_017667.2 CCDC132 Coiled-coil domain containing NM_024553 132 ENSG00000122483 NM_206886.2 CCDC18 Coiled-coil domain containing 18 ENSG00000188848 NM_207406.2 CCDC4 Coiled-coil domain containing 4 ENSG00000130783 NM_032573 CCDC62 Coiled-coil domain containing NM_201435 62 CCDC71 Coiled-coil domain containing 71 ENSG00000105321 NM_015603 CCDC9 Coiled-coil domain containing 9 ENSG00000040275 NM_017785 CCDC99 Coiled-coil domain containing 99 ENSG00000110148 NM_176875 CCKBR Cholecystokinin B receptor ENSG00000118922 NM_007249 CCL1 Chemokine (C-C motif) ligand 1 NM_016285 ENSG00000146731 NM_001009186 CCT6A Chaperonin containing TCP1, NM_001762 subunit 6A (zeta 1) ENSG00000135624 NM_001009570.1 CCT7 Chaperonin containing TCP1, NM_006429.2 subunit 7 (eta) ENSG00000177697 NM_001039490 CD151 CD151 molecule (Raph blood NM_004357 group) NM_139029 NM_139030 ENSG00000161649 NM_145273 CD300LG CD300 molecule-like family member g ENSG00000137101 NM_001782 CD72 CD72 molecule ENSG00000151465 NM_006023 CDC123 Cell division cycle 123 ENSG00000158571 NM_002625 homolog (S. cerevisiae) CDK5 Cyclin-dependent kinase 5 CDK8 Cyclin-dependent kinase 8 CDY1_HUMAN CELP Carboxyl ester lipase pseudogene ENSG00000183678 NM_001327 CENPI Centromere protein I ENSG00000184033 NM_139250 ENSG00000138092 NM_024322 CENPO Centromere protein O ENSG00000101639 NM_032142 CEP192 Centrosomal protein 192 kDa ENSG00000182923 NM_001042383.1 CEP63 Centrosomal protein 63 kDa NM_001042384.1 NM_001042400.1 NM_025180 ENSG00000101624 NM_024899 CEP76 Centrosomal protein 76 kDa ENSG00000147869 NM_005454 CER1 Cerberus 1, cysteine knot superfamily, homolog (Xenopus laevis) ENSG00000152785 NM_001201 CETN3 Centrin, EF-hand protein, 3 (CDC31 homolog, yeast) ENSG00000112175 NM_021073 CFL1 Cofilin 1 (non-muscle) ENSG00000172757 NM_005507 ENSG00000153922 NM_001270 CHD1 Chromodomain helicase DNA binding protein 1 ENSG00000131778 NM_004284 CHD1L Chromodomain helicase DNA binding protein 1-like ENSG00000111642 NM_001273 CHD4 Chromodomain helicase DNA ENSG00000152518 NM_006887 binding protein 4 ENSG00000171316 NM_017780.2 CHD7 Chromodomain helicase DNA binding protein 7 CHD9 Chromodomain helicase DNA binding protein 9 CHMP4B Chromatin modifying protein 4B CHUK Conserved helix-loop-helix ubiquitous kinase CIR_HUMAN ENSG00000134825 NM_014206 CKS2 CDC28 protein kinase regulatory subunit 2 ENSG00000109572 NM_001829 CLCN3 Chloride channel 3 NM_173872 ENSG00000166527 NM_080387 CLEC4D C-type lectin domain family 4, member D ENSG00000172243 NM_022570 CLEC7A C-type lectin domain family 7, NM_197947.2 member A NM_197948.2 NM_197950 NM_197954 ENSG00000186222 NM_018366 CNO Cappuccino homolog (mouse) ENSG00000113300 NM_015455 CNOT6 CCR4-NOT transcription complex, subunit 6 ENSG00000144619 NM_175607.1 CNTN4 Contactin 4 NM_175612.1 NM_175613 ENSG00000155052 NM_130773.2 CNTNAP5 Contactin associated protein- like 5 ENSG00000084636 NM_001856.3 COL16A1 Collagen, type XVI, alpha 1 COL20A1 Collagen, type XX, alpha 1 ENSG00000139219 NM_001844.4 COL2A1 Collagen, type II, alpha 1 NM_033150 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital) COX5B Cytochrome c oxidase subunit Vb ENSG00000160111 NM_015692.2 CPAMD8 C3 and PZP-like, alpha-2- macroglobulin domain containing 8 ENSG00000110090 NM_001031847 CPT1A Carnitine palmitoyltransferase NM_001876 1A (liver) ENSG00000060566 NM_032607 CREB3L3 CAMP responsive element binding protein 3-like 3 CRSP7 ENSG00000163254 NM_020989 CRYGC Crystallin, gamma C CSTL1 Cystatin-like 1 ENSG00000188234 NM_133446 CTGLF1 Centaurin, gamma-like family, member 1 ENSG00000163453 NM_001553 CTSA Cathepsin A ENSG00000117984 NM_001909 CTSD Cathepsin D ENSG00000173681 NM_198279 CXorf23 Chromosome X open reading frame 23 ENSG00000205666 CXorf28 Chromosome X open reading frame 28 ENSG00000101901 NM_001099922.1 CXorf45 Chromosome X open reading NM_018466 frame 45 ENSG00000176034 NM_173695 CXorf59 Chromosome X open reading frame 59 ENSG00000065615 NM_016230 CYB5R4 Cytochrome b5 reductase 4 ENSG00000108468 NM_006807 CYP3A7 Cytochrome P450, family 3, ENSG00000160870 NM_000765 subfamily A, polypeptide 7 ENSG00000186529 NM_000896 CYP4F3 Cytochrome P450, family 4, subfamily F, polypeptide 3 ENSG00000180432 NM_004391 CYP8B1 Cytochrome P450, family 8, subfamily B, polypeptide 1 ENSG00000078725 NM_014618 DBC1 Deleted in bladder cancer 1 DCC Deleted in colorectal carcinoma DCTN3 Dynactin 3 (p22) ENSG00000153904 NM_012137 DDAH1 Dimethylarginine dimethylaminohydrolase 1 ENSG00000181418 NM_015086 DDN Dendrin ENSG00000174243 NM_004818 DDX23 DEAD (Asp-Glu-Ala-Asp) box polypeptide 23 ENSG00000108654 NM_004396 DDX5 DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 ENSG00000110367 NM_004397.3 DDX6 DEAD (Asp-Glu-Ala-Asp) box polypeptide 6 ENSG00000144231 NM_004805 DEDD Death effector domain ENSG00000158796 NM_001039711 containing NM_001039712 NM_032998 ENSG00000119522 NM_020946 DENND1A DENN/MADD domain NM_024820 containing 1A ENSG00000145214 NM_001347 DGKQ Diacylglycerol kinase, theta 110 kDa ENSG00000167536 NM_144683 DHRS13 Dehydrogenase/reductase (SDR family) member 13 ENSG00000105808 NM_006989 DIP2A DIP2 disco-interacting protein 2 homolog A (Drosophila) ENSG00000107984 NM_012242 DKK1 Dickkopf homolog 1 (Xenopus laevis) ENSG00000155011 NM_014421 DKK2 Dickkopf homolog 2 (Xenopus laevis) ENSG00000161249 NM_001035516.1 DMKN Dermokine NM_033317 ENSG00000104936 NM_001081560.1 DMPK Dystrophia myotonica-protein NM_001081563.1 kinase NM_004409 ENSG00000142700 NM_032110.1 DMRTA2 DMRT-like family A2 ENSG00000172869 NM_005509 DMXL1 Dmx-like 1 ENSG00000105877 NM_003777.3 DNAH11 Dynein, axonemal, heavy ENSG00000214594 NM_018916.3 chain 11 NM_032011.1 ENSG00000137094 NM_012266 DNAJB5 DnaJ (Hsp40) homolog, subfamily B, member 5 ENSG00000169403 NM_000952 DNAJC8 DnaJ (Hsp40) homolog, subfamily C, member 8 ENSG00000197959 NM_015569.2 DNM3 Dynamin 3 ENSG00000129757 NM_000076 DNMT1 DNA (cytosine-5-)- methyltransferase 1 ENSG00000123992 NM_012100.2 DNPEP Aspartyl aminopeptidase ENSG00000130158 NM_020812.1 DOCK6 Dedicator of cytokinesis 6 ENSG00000108963 NM_001383.3 DPH1 DPH1 homolog (S. cerevisiae) ENSG00000170946 NM_181706 DPH4 DPH4, JJJ3 homolog (S. cerevisiae) DTYMK Deoxythymidylate kinase (thymidylate kinase) ENSG00000140254 NM_144565 DUOXA1 Dual oxidase maturation factor 1 ENSG00000188542 NM_001033575 DUSP28 Dual specificity phosphatase 28 ENSG00000121083 NM_080677 DYNLL2 Dynein, light chain, LC8-type 2 ENSG00000165169 NM_006520 DYNLT3 Dynein, light chain, Tctex- type 3 ENSG00000105204 NM_004714 DYRK1B Dual-specificity tyrosine-(Y)- NM_006483.1 phosphorylation regulated NM_006484 kinase 1B ENSG00000101412 NM_005225 E2F1 E2F transcription factor 1 ECEL1 Endothelin converting enzyme-like 1 ENSG00000170989 NM_001400 EDG1 Endothelial differentiation, sphingolipid G-protein- coupled receptor, 1 ENSG00000102189 NM_003566 EEA1 Early endosome antigen 1 ENSG00000153922 NM_001270 EEF1A1 Eukaryotic translation ENSG00000156508 NM_001402 elongation factor 1 alpha 1 NR_003586.1 ENSG00000165487 NM_152726 EFHA1 EF-hand domain family, member A1 ENSG00000100842 NM_005864 EFS Embryonal Fyn-associated NM_032459 substrate EGLX_HUMAN ENSG00000134698 NM_017629 EIF2C4 Eukaryotic translation initiation factor 2C, 4 EIF4E3 Eukaryotic translation initiation factor 4E family member 3 ENSG00000141642 NM_018696 ELAC1 ElaC homolog 1 (E. coli) ENSG00000162374 NM_021952 ELAVL4 ELAV (embryonic lethal, abnormal vision, Drosophila)- like 4 (Hu antigen D) ENSG00000126749 NM_006331.5 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) EML5 Echinoderm microtubule associated protein like 5 ENSG00000174837 NM_001974 EMR1 Egf-like module containing, mucin-like, hormone receptor-like 1 ENSG00000145293 NM_021204 ENOPH1 Enolase-phosphatase 1 ENSG00000136960 NM_001040092 ENPP2 Ectonucleotide NM_006209 pyrophosphatase/phosphodiesterase 2 (autotaxin) ENSG00000176177 NM_152512 ENTHD1 ENTH domain containing 1 ENSG00000054179 NM_001246 ENTPD2 Ectonucleoside triphosphate ENSG00000143032 NM_203468 diphosphohydrolase 2 NM_020063 ENSG00000134873 NM_006984 EP300 E1A binding protein p300 NM_182848 ENSG00000113946 NM_006580 EPB41L2 Erythrocyte membrane protein band 4.1-like 2 EPS15L2 ENSG00000134899 NM_000123 ERCC5 Excision repair cross- complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome)) ENSG00000143845 NM_018208 ETNK2 Ethanolamine kinase 2 ENSG00000182944 NM_005243 EWSR1 Ewing sarcoma breakpoint NM_013986 region 1 ENSG00000104313 NM_000503 EYA1 Eyes absent homolog 1 NM_172058 (Drosophila) NM_172059 NM_172060.1 ENSG00000124491 NM_000129 F13A1 Coagulation factor XIII, A1 polypeptide ENSG00000117525 NM_001993 F3 Coagulation factor III ENSG00000132259 NM_001037329 (thromboplastin, tissue factor) ENSG00000116473 NM_001010935 FARP2 FERM, RhoGEF and NM_002884 pleckstrin domain protein 2 ENSG00000124279 NM_024091 FASTKD3 FAST kinase domains 3 ENSG00000139219 NM_001844.4 FBN1 Fibrillin 1 ENSG00000166147 NM_033150 NM_000138 ENSG00000142449 NM_032447 FBN3 Fibrillin 3 ENSG00000165355 NM_203301 FBXO33 F-box protein 33 FBXO7 F-box protein 7 ENSG00000159069 NM_018998 FBXW5 F-box and WD repeat domain containing 5 FCMD ENSG00000107831 NM_006119 FGF8 Fibroblast growth factor 8 NM_033163 (androgen-induced) NM_033164 NM_033165 FHAD1 Forkhead-associated (FHA) phosphopeptide binding domain 1 ENSG00000145216 NM_030917 FIP1L1 FIP1 like 1 (S. cerevisiae) ENSG00000010932 NM_002021 FMO1 Flavin containing ENSG00000119203 NM_016207 monooxygenase 1 ENSG00000115226 NM_022823 FNDC4 Fibronectin type III domain containing 4 ENSG00000145708 NM_001882 FPGS Folylpolyglutamate synthase ENSG00000151474 NM_018027 FRMD4A FERM domain containing 4A ENSG00000166225 NM_001042555.1 FRS2 Fibroblast growth factor NM_006654.3 receptor substrate 2 ENSG00000075618 NM_003088 FSCN1 Fascin homolog 1, actin- bundling protein (Strongylocentrotus purpuratus) ENSG00000150667 NM_152597 FSIP1 Fibrous sheath interacting protein 1 ENSG00000160282 NM_006657 FTCD Formiminotransferase NM_206965 cyclodeaminase ENSG00000179163 NM_000147 FUCA1 Fucosidase, alpha-L-1, tissue ENSG00000165060 NM_000144 FXN Frataxin NM_181425.1 ENSG00000137731 NM_001680 FXYD2 FXYD domain containing ion NM_021603 transport regulator 2 ENSG00000010810 NM_002037 FYN FYN oncogene related to NM_153047 SRC, FGR, YES NM_153048 ENSG00000111432 NM_007197 FZD10 Frizzled homolog 10 (Drosophila) ENSG00000116717 NM_001924 GADD45A Growth arrest and DNA- damage-inducible, alpha ENSG00000166573 NM_001480 GALR1 Galanin receptor 1 ENSG00000140505 NM_000761 GAP43 Growth associated protein 43 ENSG00000165219 NM_015635 GAPVD1 GTPase activating protein and VPS9 domains 1 ENSG00000177628 NM_000157 GBA Glucosidase, beta; acid NM_001005741 (includes NM_001005742 glucosylceramidase) NM_001005749 NM_001005750 GCLC Glutamate-cysteine ligase, catalytic subunit ENSG00000140297 NM_004751 GCNT3 Glucosaminyl (N-acetyl) transferase 3, mucin type ENSG00000146013 NM_001496 GFRA3 GDNF family receptor alpha 3 ENSG00000167657 NM_001348 ENSG00000167925 NM_032484 GHDC GH3 domain containing GHRHR Growth hormone releasing hormone receptor ENSG00000106560 NM_015660 GIMAP2 GTPase, IMAP family ENSG00000163026 NM_025203 member 2 ENSG00000188910 NM_001005752 GJB3 Gap junction protein, beta 3, NM_024009 31 kDa ENSG00000198814 NM_000167 GK Glycerol kinase NM_203391 ENSG00000182512 NM_016417 GLRX5 Glutaredoxin 5 GOLT1A Golgi transport 1 homolog A (S. cerevisiae) ENSG00000150625 NM_005277 GPM6A Glycoprotein M6A NM_201591 NM_201592.1 GPR103 G protein-coupled receptor 103 ENSG00000069122 NM_001098518.1 GPR116 G protein-coupled receptor NM_015234 116 ENSG00000152990 NM_145290 GPR125 G protein-coupled receptor 125 ENSG00000206294 GPR143 G protein-coupled receptor 143 GPR157 G protein-coupled receptor 157 ENSG00000143147 NM_007369 GPR161 G protein-coupled receptor NM_153832 161 ENSG00000136267 NM_004080.1 GPR27 G protein-coupled receptor ENSG00000170837 NM_145695.1 27 NM_018971 ENSG00000134830 NM_018485 GPR77 G protein-coupled receptor 77 ENSG00000164199 NM_032119.3 GPR98 G protein-coupled receptor 98 ENSG00000132522 NM_004489 GPS2 G protein pathway ENSG00000181019 NM_000903 suppressor 2 NM_001025433 NM_001025434 ENSG00000211445 NM_002084.3 GPX3 Glutathione peroxidase 3 (plasma) GPX5 Glutathione peroxidase 5 (epididymal androgen-related protein) ENSG00000089351 NM_020895.2 GRAMD1A GRAM domain containing 1A ENSG00000162946 NM_001012957.1 GRB14 Growth factor receptor-bound NM_001012958 protein 14 NM_001012959 NM_018662.2 ENSG00000140307 NM_004492 GTF2A2 General transcription factor ENSG00000167968 NM_001374.2 IIA, 2, 12 kDa ENSG00000197265 NM_002095 GTF2E2 General transcription factor IIE, polypeptide 2, beta 34 kDa GTF3A General transcription factor IIIA GTPBP6 GTP binding protein 6 (putative) ENSG00000070019 NM_004963 GUCY2C Guanylate cyclase 2C (heat stable enterotoxin receptor) ENSG00000132518 NM_000180 GUCY2D Guanylate cyclase 2D, membrane (retina-specific) ENSG00000113088 NM_002104 GZMK Granzyme K (granzyme 3; tryptase II) ENSG00000128708 NM_001033085.1 HAT1 Histone acetyltransferase 1 NM_003642 ENSG00000185808 NM_153681 HBE1 Hemoglobin, epsilon 1 ENSG00000213931 NM_153682 NM_005330 ENSG00000004961 NM_005333 HCCS Holocytochrome c synthase (cytochrome c heme-lyase) hCG_1643692 ENSG00000143321 NM_004494 HDGF Hepatoma-derived growth factor (high-mobility group protein 1-like) ENSG00000169660 NM_173620.2 HEXDC Hexosaminidase (glycosyl hydrolase family 20, catalytic domain) containing ENSG00000161202 NM_004423 HHEX Hematopoietically expressed homeobox ENSG00000124440 NM_022462.3 HIF3A Hypoxia inducible factor 3, NM_152794 alpha subunit NM_152795 ENSG00000112727 NM_021018 HIST1H3H Histone cluster 1, H3h ENSG00000124693 NM_003537 ENSG00000178458 NM_003534 ENSG00000182572 NM_003533 NM_003531 NM_003532 NM_003535 NM_003530 NM_003529 NM_003536 ENSG00000204523 NM_005514 HLA-B Major histocompatibility complex, class I, B ENSG00000204525 NM_002117 HLA-C Major histocompatibility complex, class I, C HLA-DQB2 ENSG00000204632 NM_002127 HLA-G HLA-G histocompatibility ENSG00000206443 antigen, class I, G ENSG00000206506 HLA-J ENSG00000205581 NM_004965 HMGN1 High-mobility group nucleosome binding domain 1 ENSG00000103942 NM_004839.2 HOMER2 Homer homolog 2 NM_199330.1 (Drosophila) HOXA2 Homeobox A2 HOXA5 Homeobox A5 ENSG00000127483 NM_016287 HP1BP3 Heterochromatin protein 1, binding protein 3 ENSG00000110756 NM_007216 HPS5 Hermansky-Pudlak syndrome 5 NM_181507 NM_181508 HSP90B1 Heat shock protein 90 kDa beta (Grp94), member 1 IBRDC1 IDH3G Isocitrate dehydrogenase 3 (NAD+) gamma ENSG00000127415 NM_000203 IDUA Iduronidase, alpha-L- ENSG00000188483 NM_203434.2 IER5L Immediate early response 5- like ENSG00000204869 NM_001002923 IGFL4 IGF-like family member 4 ENSG00000104365 NM_001556 IKBKB Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta ENSG00000077942 NM_001996 IL15 Interleukin 15 NM_006485 NM_006486 NM_006487.2 ENSG00000177663 NM_014339 IL17RA Interleukin 17 receptor A ENSG00000115602 NM_003856 IL1RL1 Interleukin 1 receptor-like 1 NM_016232 ENSG00000016402 NM_014432 IL20RA Interleukin 20 receptor, alpha ENSG00000182393 NM_172140 IL29 Interleukin 29 (interferon, lambda 1) ENSG00000162747 INDO Indoleamine-pyrrole 2,3 dioxygenase ENSG00000128908 NM_017553 INOC1 INO80 complex homolog 1 (S. cerevisiae) ENSG00000102786 NM_001039937.1 INTS6 Integrator complex subunit 6 NM_001039938.1 NM_012141 ENSG00000119509 NM_014425 INVS Inversin NM_183245 ENSG00000120645 NM_015232 IQSEC3 IQ motif and Sec7 domain 3 ENSG00000186895 NM_005247 ITGAD Integrin, alpha D ENSG00000075388 NM_002007 ITGAE Integrin, alpha E (antigen ENSG00000083457 NM_002208 CD103, human mucosal lymphocyte antigen 1; alpha polypeptide) ENSG00000160867 NM_002011 ITGB4 Integrin, beta 4 NM_022963 NM_213647 ITGB4BP ENSG00000198399 NM_006277 ITSN2 Intersectin 2 NM_019595 NM_147152.1 ENSG00000066135 NM_014663 JMJD2A Jumonji domain containing 2A K0256_HUMAN ENSG00000173473 NM_003074 KATNA1 Katanin p60 (ATPase- ENSG00000186625 NM_007044 containing) subunit A 1 ENSG00000143603 NM_002249 KCNN3 Potassium intermediate/small NM_170782 conductance calcium- activated channel, subfamily N, member 3 ENSG00000117245 NM_020816 KIF17 Kinesin family member 17 ENSG00000130294 NM_004321.4 KIF1A Kinesin family member 1A ENSG00000143412 NM_003568 ENSG00000165115 NM_017576 KIF27 Kinesin family member 27 ENSG00000104892 NM_177417 KLC3 Kinesin light chain 3 ENSG00000163884 NM_014079 KLF15 Kruppel-like factor 15 ENSG00000138814 NM_000944 KLF4 Kruppel-like factor 4 (gut) KLF8 Kruppel-like factor 8 ENSG00000187961 NM_198317 KLHL17 Kelch-like 17 (Drosophila) ENSG00000129451 NM_001077500.1 KLK10 Kallikrein-related peptidase NM_002776 10 NM_145888 ENSG00000182481 NM_002266 KPNA2 Karyopherin alpha 2 (RAG ENSG00000215769 cohort 1, importin alpha 1) ENSG00000118162 NM_007059.2 KPTN Kaptin (actin binding protein) ENSG00000108417 NM_003770 KRT37 Keratin 37 ENSG00000186860 NM_031964 KRTAP17-1 Keratin associated protein 17-1 ENSG00000172886 NM_001012503.1 KRTAP5-9 Keratin associated protein 5-9 NM_021046.2 ENSG00000141068 NM_014238.1 KSR1 Kinase suppressor of ras 1 ENSG00000087299 NM_024884 L2HGDH L-2-hydroxyglutarate dehydrogenase L3MBTL ENSG00000167531 NM_002289 LALBA Lactalbumin, alpha- ENSG00000112769 NM_002290 LAMA4 Laminin, alpha 4 ENSG00000172037 NM_002292 LAMB2 Laminin, beta 2 (laminin S) ENSG00000005893 NM_002294 LAMP2 Lysosomal-associated NM_013995 membrane protein 2 ENSG00000107929 NM_015155 LARP5 La ribonucleoprotein domain family, member 5 ENSG00000143815 NM_002296 LBR Lamin B receptor NM_194442 ENSG00000043462 NM_005565.3 LCP2 Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76 kDa) LDOC1 Leucine zipper, down- regulated in cancer 1 ENSG00000136110 NM_001011705.1 LECT1 Leukocyte cell derived ENSG00000165349 NM_007015 chemotaxin 1 NM_001048164.1 NM_032803 ENSG00000186007 NM_001001552 LEMD1 LEM domain containing 1 ENSG00000166477 NM_138792 LEO1 Leo1, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) LETMD1 LETM1 domain containing 1 ENSG00000153902 NM_139284 LGI4 Leucine-rich repeat LGI family, member 4 LGP2_HUMAN ENSG00000070404 NM_005860 LHCGR Luteinizing ENSG00000138039 NM_000233 hormone/choriogonadotropin receptor ENSG00000143355 NM_001014434 LHX9 LIM homeobox 9 NM_020204 ENSG00000101670 NM_006033 LIPG Lipase, endothelial ENSG00000188992 NM_198996 LIPI Lipase, member I ENSG00000168216 NM_018368 LMBRD1 LMBR1 domain containing 1 ENSG00000160789 NM_005572 LMNA Lamin A/C NM_170707 NM_170708 ENSG00000072201 NM_032622 LNX1 Ligand of numb-protein X 1 ENSG00000110002 NM_014622 LOH11CR2A Loss of heterozygosity, 11, ENSG00000176920 NM_198315 chromosomal region 2, gene A NM_000511 NM_001097638.1 ENSG00000177595 NM_145886 LRDD Leucine-rich repeats and death domain containing ENSG00000081479 NM_004525 LRP2 Low density lipoprotein- related protein 2 ENSG00000125122 NM_001004055 LRRC29 Leucine rich repeat NM_012163 containing 29 ENSG00000132128 NM_006369 LRRC41 Leucine rich repeat ENSG00000163221 NM_005621 containing 41 LRRC44 Leucine rich repeat containing 44 ENSG00000197147 NM_015350 LRRC8B Leucine rich repeat containing 8 family, member B ENSG00000175928 NM_020873 LRRN1 Leucine rich repeat neuronal 1 ENSG00000149657 LSM14B LSM14B, SCD6 homolog B (S. cerevisiae) ENSG00000090006 NM_001042544.1 LTBP4 Latent transforming growth NM_001042545.1 factor beta binding protein 4 NM_003573.2 ENSG00000083099 NM_020466 LYRM2 LYR motif containing 2 ENSG00000140280 NM_153374 LYSMD2 LysM, putative peptidoglycan- binding, domain containing 2 ENSG00000163818 NM_020347 LZTFL1 Leucine zipper transcription factor-like 1 ENSG00000179632 NM_032272 MAF1 MAF1 homolog (S. cerevisiae) MAFB V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) ENSG00000068990 NM_001011548 MAGEA4 Melanoma antigen family A, 4 ENSG00000147381 NM_001011549 ENSG00000198716 NM_001011550 ENSG00000205777 NM_002362 NM_001475.1 NM_001477.1 NM_021123.2 NM_001040663.1 NM_001098406.1 NM_001098407.1 NM_001098408.1 NM_001098409.1 NM_001098410.1 NM_001098418.1 NM_001468 NM_001085441.1 NM_001098405.1 NM_001474.1 NM_001476.1 ENSG00000177383 NM_022149 MAGEF1 Melanoma antigen family F, 1 ENSG00000135040 NM_024635 MAK10 MAK10 homolog, amino-acid N-acetyltransferase subunit, (S. cerevisiae) ENSG00000196782 NM_018717.3 MAML3 Mastermind-like 3 (Drosophila) ENSG00000130758 NM_002446 MAP3K10 Mitogen-activated protein kinase kinase kinase 10 ENSG00000085511 NM_005922 MAP3K4 Mitogen-activated protein NM_006724 kinase kinase kinase 4 ENSG00000100324 NM_006116 MAP3K7IP1 Mitogen-activated protein NM_153497 kinase kinase kinase 7 interacting protein 1 ENSG00000128310 NM_003614 MAP4 Microtubule-associated protein 4 ENSG00000104814 NM_001042600.1 MAP4K1 Mitogen-activated protein NM_007181.4 kinase kinase kinase kinase 1 ENSG00000164114 NM_001039580 MAP9 Microtubule-associated protein 9 ENSG00000116141 NM_018650 MARK1 MAP/microtubule affinity- regulating kinase 1 MBIP MAP3K12 binding inhibitory protein 1 ENSG00000160294 NM_003906 MCM3AP Minichromosome ENSG00000171314 NM_002629 maintenance complex component 3 associated protein ENSG00000112139 NM_153487.3 MDGA1 MAM domain containing glycosylphosphatidylinositol anchor 1 ENSG00000184634 NM_005120.2 MED12 Mediator complex subunit 12 ENSG00000144893 NM_053002 MED12L Mediator complex subunit 12- like ENSG00000156603 NM_153450 MED19 Mediator complex subunit 19 ENSG00000123600 NM_024770 METTL8 Methyltransferase like 8 ENSG00000135953 NM_032718 MFSD9 Major facilitator superfamily domain containing 9 ENSG00000198160 NM_001077700.1 MIER1 Mesoderm induction early NM_001077701.1 response 1 homolog NM_001077702.1 (Xenopus laevis) NM_001077703.1 NM_001077704.1 NM_020948.2 ENSG00000099964 NM_002415 MIF Macrophage migration inhibitory factor (glycosylation-inhibiting factor) ENSG00000099875 NM_017572 MKNK2 MAP kinase interacting NM_199054 serine/threonine kinase 2 ENSG00000089693 NM_005439 MLF2 Myeloid leukemia factor 2 ENSG00000076242 NM_000249 MLH1 MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) MLLT10 Myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 10 ENSG00000115648 NM_001042467.1 MLPH Melanophilin NM_024101 ENSG00000142606 NM_033467 MMEL1 Membrane metallo- endopeptidase-like 1 ENSG00000106571 NM_000168 MMP10 Matrix metallopeptidase 10 (stromelysin 2) ENSG00000137745 NM_002427 MMP13 Matrix metallopeptidase 13 (collagenase 3) MND1 Meiotic nuclear divisions 1 homolog (S. cerevisiae) ENSG00000138587 NM_018365 MNS1 Meiosis-specific nuclear structural 1 ENSG00000165943 NM_022151 MOAP1 Modulator of apoptosis 1 MOB2_HUMAN ENSG00000182890 NM_012084 MOBP Myelin-associated oligodendrocyte basic protein ENSG00000075643 NM_017947 MOCOS Molybdenum cofactor sulfurase ENSG00000172680 NM_005372 MOS V-mos Moloney murine sarcoma viral oncogene homolog ENSG00000107186 NM_003829.3 MPDZ Multiple PDZ domain protein ENSG00000158186 NM_001085049.1 MRAS Muscle RAS oncogene NM_012219 homolog ENSG00000134042 NM_031939 MRO Maestro ENSG00000086504 NM_006428 MRPL28 Mitochondrial ribosomal protein L28 ENSG00000055950 NM_032112 MRPL43 Mitochondrial ribosomal NM_176792 protein L43 NM_176793 NM_176794 ENSG00000143436 NM_031420 MRPL9 Mitochondrial ribosomal protein L9 ENSG00000048544 NM_018141 MRPS10 Mitochondrial ribosomal protein S10 ENSG00000163319 NM_016067 MRPS18C Mitochondrial ribosomal protein S18C ENSG00000144029 NM_031902 MRPS5 Mitochondrial ribosomal protein S5 ENSG00000095002 NM_000251 MSH2 MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) ENSG00000172209 NM_005295 MSMB Microseminoprotein, beta- ENSG00000173531 NM_020998 MST1 Macrophage stimulating 1 (hepatocyte growth factor- like) ENSG00000188786 NM_005955 MTF1 Metal-regulatory transcription factor 1 MTHFD1L Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like ENSG00000063601 NM_003828 MTMR1 Myotubularin related protein 1 ENSG00000163719 NM_001077525.1 MTMR14 Myotubularin related protein NM_001077526.1 14 NM_022485.3 ENSG00000170873 NM_014751 MTSS1 Metastasis suppressor 1 ENSG00000063515 NM_005315 MYCN V-myc myelocytomatosis viral ENSG00000134323 NM_005378 related oncogene, neuroblastoma derived (avian) ENSG00000172428 NM_138336 MYEOV2 Myeloma overexpressed 2 MYH13 MYO15B Myosin XVB pseudogene ENSG00000041515 NM_015011 MYO16 Myosin XVI ENSG00000142661 NM_152372.3 MYOM3 Myomesin family, member 3 ENSG00000090971 NM_020378 NAT14 N-acetyltransferase 14 ENSG00000144035 NM_003960 NAT8B N-acetyltransferase 8B NM_016347.2 (gene/pseudogene) ENSG00000215691 NBR1 Neighbor of BRCA1 gene 1 ENSG00000025770 NM_014551.4 NCAPH2 Non-SMC condensin II NM_152299 complex, subunit H2 ENSG00000198646 NM_014071 NCOA6 Nuclear receptor coactivator 6 ENSG00000166579 NM_001025579 NDEL1 NudE nuclear distribution NM_030808 gene E homolog (A. nidulans)- like 1 ENSG00000124479 NM_000266 NDP Norrie disease (pseudoglioma) ENSG00000158864 NM_004550 NDUFS2 NADH dehydrogenase (ubiquinone) Fe—S protein 2, 49 kDa (NADH-coenzyme Q reductase) ENSG00000109674 NM_018248 NEIL3 Nei endonuclease VIII-like 3 (E. coli) ENSG00000197168 NM_199289 NEK5 NIMA (never in mitosis gene a)-related kinase 5 ENSG00000072736 NM_004555 NFATC3 Nuclear factor of activated T- NM_173163 cells, cytoplasmic, NM_173164.1 calcineurin-dependent 3 NM_173165 ENSG00000050344 NM_004289 NFE2L3 Nuclear factor (erythroid- ENSG00000124212 NM_000961 derived 2)-like 3 ENSG00000124529 NM_003544 NFKBIE Nuclear factor of kappa light ENSG00000146232 NM_004556 polypeptide gene enhancer in ENSG00000158406 NM_003543 B-cells inhibitor, epsilon ENSG00000182217 NM_001034077 NM_003548 NM_003539 NM_003538 NM_003542 NM_021968 NM_175054 NM_003541 NM_003540 NM_003495 NM_003545 NM_003546 ENSG00000167984 NM_178844.2 NLRC3 NLR family, CARD domain containing 3 ENSG00000179873 NM_145007 NLRP11 NLR family, pyrin domain containing 11 ENSG00000160703 NM_024618 NLRX1 NLR family member X1 NM_170722.1 NME7 — NMI N-myc (and STAT) interactor ENSG00000183691 NM_005450 NOG Noggin ENSG00000130935 NM_015462 NOL11 Nucleolar protein 11 ENSG00000128731 NM_004667 NPHS1 Nephrosis 1, congenital, Finnish type (nephrin) ENSG00000187258 NM_207172 NPSR1 Neuropeptide S receptor 1 NM_207173 ENSG00000156642 NM_012428 NPTN Neuroplastin NM_017455 ENSG00000181019 NM_000903 NQO1 NAD(P)H dehydrogenase, NM_001025433 quinone 1 NM_001025434 NR_002593.1 ENSG00000148572 NM_030759 NRBF2 Nuclear receptor binding factor 2 ENSG00000169752 NM_138573 NRG4 Neuregulin 4 ENSG00000173566 NM_024815.3 NUDT18 Nudix (nucleoside diphosphate linked moiety X)- type motif 18 ENSG00000167799 NM_181843 NUDT8 Nudix (nucleoside diphosphate linked moiety X)- type motif 8 ENSG00000136243 NM_007342 NUPL2 Nucleoporin like 2 NXF3 Nuclear RNA export factor 3 O95431_HUMAN ENSG00000135114 NM_003733 OASL 2′-5′-oligoadenylate NM_198213 synthetase-like ENSG00000132297 NM_001080399.1 OC90 Otoconin 90 ODZ3 Odz, odd Oz/ten-m homolog 3 (Drosophila) ENSG00000181355 NM_153003 OFCC1 Orofacial cleft 1 candidate 1 ENSG00000011083 NM_014228 OGFR Opioid growth factor receptor ENSG00000060491 NM_007346 ENSG00000162745 NM_015441 OLFML2B Olfactomedin-like 2B OPRM1 Opioid receptor, mu 1 ENSG00000198965 NM_001004472 OR10R2 Olfactory receptor, family 10, subfamily R, member 2 ENSG00000203662 NR_002141.1 OR2M1P Olfactory receptor, family 2, subfamily M, member 1 pseudogene ENSG00000177186 NM_001004691 OR2M7 Olfactory receptor, family 2, subfamily M, member 7 ENSG00000122718 NM_019897 OR2S2 Olfactory receptor, family 2, subfamily S, member 2 ENSG00000180934 NM_001001917 OR56A1 Olfactory receptor, family 56, subfamily A, member 1 ENSG00000148215 NM_001001923 OR5C1 Olfactory receptor, family 5, subfamily C, member 1 ENSG00000179420 NR_002140.1 OR6W1P Olfactory receptor, family 6, subfamily W, member 1 pseudogene ENSG00000144909 NM_022776 OSBPL11 Oxysterol binding protein-like 11 ENSG00000134996 NM_012383 OSTF1 Osteoclast stimulating factor 1 ENSG00000036473 NM_000531 OTC Ornithine ENSG00000149948 NM_003484 carbamoyltransferase ENSG00000068308 NM_017602 OTUD5 OTU domain containing 5 ENSG00000187950 NM_183378.2 OVCH1 Ovochymase 1 ENSG00000187848 NM_012226 P2RX2 Purinergic receptor P2X, NM_016318 ligand-gated ion channel, 2 NM_170682 NM_170683 NM_174872 NM_174873 ENSG00000171631 NM_004154 P2RY6 Pyrimidinergic receptor P2Y, NM_176796 G-protein coupled, 6 NM_176797 NM_178798 ENSG00000112530 NM_001080378.1 PACRG PARK2 co-regulated NM_001080379.1 NM_152410 ENSG00000198682 NM_001015880.1 PAPSS2 3′-phosphoadenosine 5′- NM_004670 phosphosulfate synthase 2 ENSG00000140694 NM_002582.1 PARN Poly(A)-specific ribonuclease (deadenylation nuclease) ENSG00000148600 NM_033100 PCDH21 Protocadherin 21 ENSG00000120265 NM_005389 PCMT1 Protein-L-isoaspartate (D- aspartate) O- methyltransferase ENSG00000135749 NM_014801.3 PCNXL2 Pecanex-like 2 (Drosophila) ENSG00000173282 PCNXL3 Pecanex-like 3 (Drosophila) ENSG00000197136 ENSG00000099783 NM_005968 PCSK6 Proprotein convertase ENSG00000140479 NM_031203 subtilisin/kexin type 6 NM_002570.3 NM_138319.2 NM_138320.1 NM_138321.1 NM_138322.2 NM_138323.1 NM_138324.1 NM_138325.2 ENSG00000102230 NM_004845 PCYT1B Phosphate cytidylyltransferase 1, choline, beta ENSG00000154678 NM_005020 PDE1C Phosphodiesterase 1C, calmodulin-dependent 70 kDa ENSG00000121905 NM_002143 PDE4D Phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) ENSG00000167004 NM_005313 PDIA3 Protein disulfide isomerase family A, member 3 PDK3 Pyruvate dehydrogenase kinase, isozyme 3 ENSG00000125430 NM_006041 PFAS Phosphoribosylformylglycinamidine synthase (FGAR amidotransferase) ENSG00000170525 NM_004566 PFKFB3 6-phosphofructo-2- kinase/fructose-2,6- biphosphatase 3 ENSG00000025293 NM_016436 PHF20 PHD finger protein 20 ENSG00000172943 NM_015107 PHF8 PHD finger protein 8 ENSG00000144381 NM_002156 PHKG2 Phosphorylase kinase, ENSG00000156873 NM_199440 gamma 2 (testis) NM_000294 ENSG00000087111 NM_033198 PIGS Phosphatidylinositol glycan anchor biosynthesis, class S ENSG00000121879 NM_006218.2 PIK3CA Phosphoinositide-3-kinase, catalytic, alpha polypeptide PIK4CA ENSG00000107959 NM_014889.2 PITRM1 Pitrilysin metallopeptidase 1 ENSG00000197181 NM_018068 PIWIL2 Piwi-like 2 (Drosophila) ENSG00000118762 NM_000297 PKD2 Polycystic kidney disease 2 (autosomal dominant) ENSG00000143627 NM_000298 PKLR Pyruvate kinase, liver and NM_181871.2 RBC ENSG00000116711 NM_024420 PLA2G4A Phospholipase A2, group IVA (cytosolic, calcium- dependent) ENSG00000168907 NM_213600 PLA2G4F Phospholipase A2, group IVF ENSG00000127472 NM_000929 PLA2G5 Phospholipase A2, group V ENSG00000137055 NM_001031689 PLAA Phospholipase A2-activating NM_004253 protein PLEKHQ1 PLGB_HUMAN PLGLA1 Plasminogen-like A1 ENSG00000003147 NM_004968 PLGLB1 Plasminogen-like B1 ENSG00000125551 NM_022307 ENSG00000183281 NM_002665 NM_001032392 PLSCR5 Phospholipid scramblase family, member 5 ENSG00000127957 NM_001003686 PMS2L3 Postmeiotic segregation NM_005395 increased 2-like 3 ENSG00000146453 NM_173516 PNLDC1 Poly(A)-specific ribonuclease (PARN)-like domain containing 1 ENSG00000177666 NM_020376 PNPLA2 Patatin-like phospholipase domain containing 2 ENSG00000032444 NM_006702 PNPLA6 Patatin-like phospholipase domain containing 6 ENSG00000146278 NM_006813 PNRC1 Proline-rich nuclear receptor coactivator 1 ENSG00000189266 NM_017761 PNRC2 Proline-rich nuclear receptor ENSG00000215700 coactivator 2 ENSG00000047315 NM_000938 POLR2B Polymerase (RNA) II (DNA directed) polypeptide B, 140 kDa ENSG00000172336 NM_005837 POP7 Processing of precursor 7, ribonuclease P/MRP subunit (S. cerevisiae) PPAP2C Phosphatidic acid phosphatase type 2C PPIB Peptidylprolyl isomerase B (cyclophilin B) ENSG00000084072 NM_006112 PPIE Peptidylprolyl isomerase E NM_203456 (cyclophilin E) NM_203457.1 ENSG00000156475 NM_004576 PPP2R2B Protein phosphatase 2 NM_181674 (formerly 2A), regulatory NM_181675 subunit B, beta isoform NM_181676 NM_181677.1 NM_181678.1 ENSG00000204481 NM_001099854.1 PRAMEF14 PRAME family member 14 ENSG00000106617 NM_001040633.1 PRKAG2 Protein kinase, AMP- NM_016203 activated, gamma 2 non- NM_024429.1 catalytic subunit ENSG00000067606 NM_001033581.1 PRKCZ Protein kinase C, zeta NM_001033582.1 NM_002744 ENSG00000138669 NM_006259 PRKG2 Protein kinase, cGMP- dependent, type II PROM1 Prominin 1 ENSG00000197746 NM_001042465.1 PSAP Prosaposin (variant Gaucher NM_001042466.1 disease and variant NM_002778 metachromatic leukodystrophy) ENSG00000100055 NM_013385 PSCD4 Pleckstrin homology, Sec7 and coiled-coil domains 4 ENSG00000142507 NM_002798 PSMB6 Proteasome (prosome, macropain) subunit, beta type, 6 PSMC3IP ENSG00000173692 NM_002807 PSMD1 Proteasome (prosome, macropain) 26S subunit, non- ATPase, 1 ENSG00000095261 NM_005047 PSMD5 Proteasome (prosome, macropain) 26S subunit, non- ATPase, 5 ENSG00000121390 NM_001042414.1 PSPC1 Paraspeckle component 1 NR_003272.1 ENSG00000125384 NM_000956 PTGER2 Prostaglandin E receptor 2 (subtype EP2), 53 kDa ENSG00000175354 NM_002828 PTPN2 Protein tyrosine phosphatase, NM_080422 non-receptor type 2 NM_080423 PXMP2 Peroxisomal membrane protein 2, 22 kDa ENSG00000041353 NM_004163 RAB27B RAB27B, member RAS oncogene family ENSG00000109113 NM_031934 RAB34 RAB34, member RAS oncogene family ENSG00000179331 NM_017516 RAB39 RAB39, member RAS oncogene family ENSG00000172780 NM_020701.2 RAB43 RAB43, member RAS NM_198490 oncogene family ENSG00000137955 NM_004582 RABGGTB Rab geranylgeranyltransferase, beta subunit RAC2 Ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) ENSG00000051180 NM_002875 RAD51 RAD51 homolog (RecA NM_133487.2 homolog, E. coli) (S. cerevisiae) ENSG00000185379 NM_002878 RAD51L3 RAD51-like 3 (S. cerevisiae) NM_133629 ENSG00000155918 NM_130900 RAET1L Retinoic acid early transcript 1L ENSG00000175097 NM_000536 RAG2 Recombination activating gene 2 ENSG00000080823 NM_014226 RAGE Renal tumor antigen ENSG00000124233 NM_003007 RAI2 Retinoic acid induced 2 ENSG00000131831 NM_198139.1 NM_021785 ENSG00000125970 NM_007367 RALY RNA binding protein, NM_016732 autoantigenic (hnRNP- associated with lethal yellow homolog (mouse)) ENSG00000076864 NM_002885 RAP1GAP RAP1 GTPase activating protein ENSG00000111344 NM_004658 RASAL1 RAS protein activator like 1 (GAP1 like) ENSG00000107551 NM_032023 RASSF4 Ras association (RalGDS/AF- 6) domain family 4 ENSG00000122257 NM_006910 RBBP6 Retinoblastoma binding NM_018703 protein 6 ENSG00000179051 NM_018715 RCC2 Regulator of chromosome condensation 2 ENSG00000160957 NM_004260.2 RECQL4 RecQ protein-like 4 RG9MTD1 RNA (guanine-9-) methyltransferase domain containing 1 ENSG00000158315 NM_017821 RHBDL2 Rhomboid, veinlet-like 2 (Drosophila) ENSG00000187010 NM_016124 RHD Rh blood group, D antigen RHOT2 Ras homolog gene family, member T2 ENSG00000176406 NM_014677.3 RIMS2 Regulating synaptic membrane exocytosis 2 ENSG00000153561 NM_022780 RMND5A Required for meiotic nuclear division 5 homolog A (S. cerevisiae) ENSG00000137075 NM_022781 RNF38 Ring finger protein 38 NM_194328 NM_194329 NM_194330 NM_194332 ENSG00000169855 NM_002941.2 ROBO1 Roundabout, axon guidance NM_133631.1 receptor, homolog 1 (Drosophila) ENSG00000161016 NM_000973 RPL8 Ribosomal protein L8 NM_033301 ENSG00000124614 NM_001014 RPS10 Ribosomal protein S10 ENSG00000177606 NM_002228 ENSG00000166133 NM_152260 RPUSD2 RNA pseudouridylate synthase domain containing 2 ENSG00000144580 NM_005444 RQCD1 RCD1 required for cell differentiation1 homolog (S. pombe) ENSG00000083750 NM_006064 RRAGB Ras-related GTP binding B NM_016656 RSBN1L Round spermatid basic protein 1-like RSHL2 ENSG00000115310 NM_007008.2 RTN4 Reticulon 4 NM_020532.4 NM_153828 NM_207520.1 NM_207521 ENSG00000133105 NM_130806 RXFP2 Relaxin/insulin-like family peptide receptor 2 ENSG00000188015 NM_002960 S100A3 S100 calcium binding protein A3 S100A7A S100 calcium binding protein A7A ENSG00000151835 NM_014363 SACS Spastic ataxia of Charlevoix- Saguenay (sacsin) ENSG00000203943 NM_001010971 SAMD13 Sterile alpha motif domain containing 13 ENSG00000161526 NM_013260 SAP30BP SAP30 binding protein ENSG00000189001 NM_198538 SBSN Suprabasin SCAMP2 Secretory carrier membrane protein 2 ENSG00000114650 NM_012235 SCAP SREBF chaperone ENSG00000173572 NM_176810 ENSG00000136448 NM_021079 SCG2 Secretogranin II ENSG00000171951 NM_003469 (chromogranin C) ENSG00000079689 NM_006998 SCGN Secretagogin, EF-hand ENSG00000153253 NM_006922 calcium binding protein ENSG00000102098 NM_006089 SCML2 Sex comb on midleg-like 2 ENSG00000134419 NM_001019 (Drosophila) NM_001030009 ENSG00000215767 NM_012313.1 SCN9A Sodium channel, voltage- NM_014512.1 gated, type IX, alpha subunit NM_014513.2 ENSG00000080293 NM_002980 SCTR Secretin receptor ENSG00000133116 NM_004795 ENSG00000140612 NM_014300.2 SEC11A SEC11 homolog A (S. cerevisiae) ENSG00000188404 NM_000655.3 SELL Selectin L (lymphocyte adhesion molecule 1) ENSG00000174175 NM_003005 SELP Selectin P (granule membrane protein 140 kDa, antigen CD62) ENSG00000112701 NM_001100409.1 SENP6 SUMO1/sentrin specific ENSG00000144659 NM_015571.2 peptidase 6 NM_017875 SERPINE2 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 ENSG00000149212 NM_144665 SESN3 Sestrin 3 ENSG00000104897 NM_007165 SF3A2 Splicing factor 3a, subunit 2, 66 kDa ENSG00000116754 NM_004768 SFRS11 Splicing factor, arginine/serine-rich 11 ENSG00000139218 NM_004719 SFRS2IP Splicing factor, arginine/serine-rich 2, interacting protein SG494_HUMAN ENSG00000160410 NM_138392 SHKBP1 SH3KBP1 binding protein 1 ENSG00000112246 NM_005068 SIM1 Single-minded homolog 1 ENSG00000135862 NM_002293 (Drosophila) ENSG00000089163 NM_012240 SIRT4 Sirtuin (silent mating type ENSG00000164303 NM_153343 information regulation 2 homolog) 4 (S. cerevisiae) ENSG00000077463 NM_016539 SIRT6 Sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) ENSG00000187531 NM_016538 SIRT7 Sirtuin (silent mating type information regulation 2 homolog) 7 (S. cerevisiae) ENSG00000126903 NM_019848 SLC10A3 Solute carrier family 10 (sodium/bile acid cotransporter family), member 3 ENSG00000145283 NM_197965 SLC10A6 Solute carrier family 10 (sodium/bile acid cotransporter family), member 6 ENSG00000139370 NM_145648 SLC15A4 Solute carrier family 15, member 4 ENSG00000102743 NM_014252 SLC25A15 Solute carrier family 25 (mitochondrial carrier; ornithine transporter) member 15 ENSG00000125648 NM_024103 SLC25A23 Solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23 ENSG00000153046 NM_004824 SLC26A3 Solute carrier family 26, NM_170751.1 member 3 NM_170752 ENSG00000008300 NM_001040454.1 SLC26A6 Solute carrier family 26, NM_001407 member 6 NM_022911.2 NM_134263.2 NM_134426.2 ENSG00000169359 NM_004733 SLC33A1 Solute carrier family 33 (acetyl-CoA transporter), member 1 ENSG00000175782 NM_018656.2 SLC35E3 Solute carrier family 35, member E3 ENSG00000141424 NM_001099406.1 SLC39A6 Solute carrier family 39 (zinc NM_012319.3 transporter), member 6 SLC5A3 ENSG00000170920 NM_001001958 SMARCA5 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5 ENSG00000146830 NM_022574 SMC3 Structural maintenance of chromosomes 3 ENSG00000102172 NM_004595 SMS Spermine synthase SNAPAP ENSG00000205302 NM_003100 SNX2 Sorting nexin 2 SNX3 Sorting nexin 3 ENSG00000115904 NM_005633 SOS1 Son of sevenless homolog 1 (Drosophila) SOS2 Son of sevenless homolog 2 (Drosophila) ENSG00000123352 NM_023071 SPATS2 Spermatogenesis associated, serine-rich 2 SPESP1 ENSG00000147059 NM_019003 SPIN2A Spindlin family, member 2A SPINT4 Serine peptidase inhibitor, Kunitz type 4 ENSG00000188766 NM_001039616.1 SPRED3 Sprouty-related, EVH1 NM_001042522.1 domain containing 3 ENSG00000070182 NM_000347 SPTB Spectrin, beta, erythrocytic NM_001024858 (includes spherocytosis, clinical type I) ENSG00000213523 NM_001035235 SRA1 Steroid receptor RNA activator 1 SRP9 Signal recognition particle 9 kDa ENSG00000135250 NM_182691 SRPK2 SFRS protein kinase 2 NM_182692 ENSG00000138385 NM_003142 SSB Sjogren syndrome antigen B (autoantigen La) ENSG00000160075 NM_014188 SSU72 SSU72 RNA polymerase II CTD phosphatase homolog (S. cerevisiae) ENSG00000117155 NM_014021 SSX2IP Synovial sarcoma, X breakpoint 2 interacting protein ENSG00000115525 NM_001042437.1 ST3GAL5 ST3 beta-galactoside alpha- NM_003896 2,3-sialyltransferase 5 ENSG00000177511 NM_015879 ST8SIA3 ST8 alpha-N-acetyl- neuraminide alpha-2,8- sialyltransferase 3 ENSG00000101972 NM_001042749.1 STAG2 Stromal antigen 2 NM_001042750.1 NM_001042751.1 NM_006603 ENSG00000066923 NM_012447 STAG3 Stromal antigen 3 STAP1_HUMAN ENSG00000124214 NM_001037328 STAU1 Staufen, RNA binding protein, ENSG00000185022 NM_004602 homolog 1 (Drosophila) NM_017452 NM_017453 NM_017454 NM_012323 NM_152878 ENSG00000117632 NM_005563 STMN1 Stathmin 1/oncoprotein 18 NM_203399 NM_203401 STRA13 Stimulated by retinoic acid 13 homolog (mouse) ENSG00000137868 NM_022369 STRA6 Stimulated by retinoic acid gene 6 homolog (mouse) STX4 Syntaxin 4 ENSG00000076944 NM_006949 STXBP2 Syntaxin binding protein 2 ENSG00000164506 NM_139244 STXBP5 Syntaxin binding protein 5 (tomosyn) SUCLG1 Succinate-CoA ligase, GDP- forming, alpha subunit ENSG00000088002 NM_004605 SULT2B1 Sulfotransferase family, NM_177973 cytosolic, 2B, member 1 ENSG00000106868 NM_022486 SUSD1 Sushi domain containing 1 ENSG00000179751 NM_001080468.1 SYCN Syncollin SYNC1 Syncoilin, intermediate filament 1 ENSG00000159082 NM_003895 SYNJ1 Synaptojanin 1 NM_203446 ENSG00000163630 NM_144642.3 SYNPR Synaptoporin ENSG00000006432 NM_033141 SYT5 Synaptotagmin V ENSG00000129990 NM_003180 ENSG00000134207 NM_205848 SYT6 Synaptotagmin VI ENSG00000176358 NM_001077503.1 TAC4 Tachykinin 4 (hemokinin) NM_001077504.1 NM_001077505.1 NM_001077506.1 NM_170685.2 ENSG00000141384 NM_005640.1 TAF4B TAF4b RNA polymerase II, TATA box binding protein (TBP)-associated factor, 105 kDa ENSG00000206233 TAP1 Transporter 1, ATP-binding ENSG00000206297 cassette, sub-family B (MDR/TAP) ENSG00000179002 NM_152232 TAS1R2 Taste receptor, type 1, member 2 ENSG00000121318 NM_023921 TAS2R10 Taste receptor, type 2, member 10 ENSG00000106052 NM_001079864.1 TAX1BP1 Tax1 (human T-cell leukemia NM_006024 virus type I) binding protein 1 ENSG00000131374 NM_014744 TBC1D5 TBC1 domain family, member 5 ENSG00000132561 NM_002380.3 TBP TATA box binding protein NM_030583.2 ENSG00000136270 NM_004749 TBRG4 Transforming growth factor NM_030900 beta regulator 4 NM_199122 ENSG00000059377 NM_001061 TBXAS1 Thromboxane A synthase 1 NM_030984 (platelet, cytochrome P450, family 5, subfamily A) ENSG00000133142 NM_001006935.1 TCEAL4 Transcription elongation NM_001006936.1 factor A (SII)-like 4 NM_001006937.1 NM_024863 ENSG00000148737 NM_030756 TCF7L2 Transcription factor 7-like 2 (T-cell specific, HMG-box) ENSG00000120156 NM_000459 TEK TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal) ENSG00000132604 NM_005652 TERF2 Telomeric repeat binding factor 2 ENSG00000100109 NM_001008697 TFIP11 Tuftelin interacting protein 11 NM_012143 ENSG00000092295 NM_000359 TGM1 Transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma- glutamyltransferase) ENSG00000180176 NM_000360 TH Tyrosine hydroxylase NM_199292 NM_199293 ENSG00000143198 NM_004528 THOP1 Thimet oligopeptidase 1 ENSG00000172009 NM_003249 ENSG00000179886 NM_032862 TIGD5 Tigger transposable element derived 5 ENSG00000071242 NM_001006932 TIMM23 Translocase of inner ENSG00000138297 NM_021135 mitochondrial membrane 23 NM_006327 homolog (yeast) TLE4 Transducin-like enhancer of split 4 (E(sp1) homolog, Drosophila) ENSG00000162604 NM_032027.2 TM2D1 TM2 domain containing 1 ENSG00000136404 NM_023003 TM6SF1 Transmembrane 6 superfamily member 1 TMEM112B TMEM128 Transmembrane protein 128 ENSG00000161558 NM_018273 TMEM143 Transmembrane protein 143 ENSG00000168890 NM_001031738 TMEM150 Transmembrane protein 150 NM_153342 ENSG00000166822 NM_145254 TMEM170 Transmembrane protein 170 TMEM177 Transmembrane protein 177 ENSG00000177854 NM_003492 TMEM187 Transmembrane protein 187 TMEM49 Transmembrane protein 49 ENSG00000118600 NM_014254 TMEM5 Transmembrane protein 5 ENSG00000142188 NM_006134 TMEM50B Transmembrane protein 50B ENSG00000121900 NM_033504 TMEM54 Transmembrane protein 54 ENSG00000116857 NM_016456 TMEM9 Transmembrane protein 9 ENSG00000175348 NM_020644 TMEM9B TMEM9 domain family, member B ENSG00000178297 NM_182973 TMPRSS9 Transmembrane protease, serine 9 ENSG00000034510 NM_021103 TMSB10 Thymosin, beta 10 TMSL1 Thymosin-like 1 ENSG00000026036 NM_003823 TNFRSF6B Tumor necrosis factor NM_016434 receptor superfamily, NM_032945 member 6b, decoy NM_032957 ENSG00000131165 NM_001083314.1 TNFSF14 Tumor necrosis factor NM_002768.2 (ligand) superfamily, member 14 ENSG00000168884 NM_024309 TNIP2 TNFAIP3 interacting protein 2 TNPO2 Transportin 2 (importin 3, karyopherin beta 2b) ENSG00000090905 NM_014494 TNRC6A Trinucleotide repeat containing 6A ENSG00000079308 NM_022648 TNS1 Tensin 1 ENSG00000196655 NM_016146 TRAPPC4 Trafficking protein particle complex 4 TRAV24 TRBV10-1 TRBV4-3 ENSG00000213689 NM_016381.3 TREX1 Three prime repair NM_033627 exonuclease 1 NM_033628 NM_033629 ENSG00000137394 NM_006778 TRIM10 Tripartite motif-containing 10 ENSG00000204613 NM_052828 ENSG00000206424 ENSG00000134253 NM_025188 TRIM45 Tripartite motif-containing 45 ENSG00000163462 NM_025058 TRIM46 Tripartite motif-containing 46 ENSG00000070985 NM_014555 TRPM5 Transient receptor potential cation channel, subfamily M, member 5 ENSG00000104447 NW_014112 TRPS1 Trichorhinophalangeal syndrome I ENSG00000111199 NM_021625 TRPV4 Transient receptor potential NM_147204 cation channel, subfamily V, member 4 ENSG00000103197 NM_000548 TSC2 Tuberous sclerosis 2 NM_021055 ENSG00000074319 NM_006292 TSG101 Tumor susceptibility gene 101 ENSG00000171045 NM_145003 TSNARE1 T-SNARE domain containing 1 ENSG00000064201 NM_005705.4 TSPAN32 Tetraspanin 32 NM_139022 ENSG00000163728 NM_001042601.1 TTC14 Tetratricopeptide repeat NM_133462 domain 14 ENSG00000176014 NM_032525 TUBB6 Tubulin, beta 6 ENSG00000074935 NM_016262 TUBE1 Tubulin, epsilon 1 ENSG00000104723 NM_006765 TUSC3 Tumor suppressor candidate 3 NM_178234 U464_HUMAN ENSG00000125976 NM_006047 UBAP2L Ubiquitin associated protein ENSG00000143569 NM_152838 2-like NM_014847 ENSG00000170035 NM_006357 UBE2E4P Ubiquitin-conjugating enzyme NM_182678 E2E 4 pseudogene ENSG00000175564 NM_003356 UCP3 Uncoupling protein 3 NM_022803.1 (mitochondrial, proton carrier) ENSG00000102595 NM_020121 UGCGL2 UDP-glucose ceramide glucosyltransferase-like 2 UGT1A1 ENSG00000135226 NM_053039 UGT2B28 UDP glucuronosyltransferase 2 family, polypeptide B28 ENSG00000147854 NM_152896 UHRF2 Ubiquitin-like, containing PHD and RING finger domains, 2 ENSG00000111981 NM_025218 ULBP1 UL16 binding protein 1 ENSG00000131015 NM_025217 ULBP2 UL16 binding protein 2 ENSG00000182168 NM_003728 UNC5C Unc-5 homolog C (C. elegans) ENSG00000164405 NM_014402 UQCRQ Ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5 kDa ENSG00000159650 NM_144639 UROC1 Urocanase domain containing 1 ENSG00000158773 NM_007122 USF1 Upstream transcription factor 1 NM_207005.1 ENSG00000135093 NM_032663 USP30 Ubiquitin specific peptidase 30 ENSG00000170185 NM_032557 USP38 Ubiquitin specific peptidase 38 ENSG00000168883 NM_006590 USP39 Ubiquitin specific peptidase 39 ENSG00000170242 NM_017944.3 USP47 Ubiquitin specific peptidase 47 USP7 Ubiquitin specific peptidase 7 (herpes virus-associated) ENSG00000198382 NM_003369 UVRAG UV radiation resistance associated gene ENSG00000103043 NM_018052 VAC14 Vac14 homolog (S. cerevisiae) ENSG00000111786 NM_003769 VAMP5 Vesicle-associated ENSG00000168899 NM_006634 membrane protein 5 (myobrevin) ENSG00000162692 NM_001078 VCAM1 Vascular cell adhesion NM_080682 molecule 1 ENSG00000147852 NM_001018056 VLDLR Very low density lipoprotein NM_003383 receptor ENSG00000197969 NM_001018037.1 VPS13A Vacuolar protein sorting 13 NM_001018038.1 homolog A (S. cerevisiae) NM_015186 NM_033305 ENSG00000104142 NM_020857 VPS18 Vacuolar protein sorting 18 homolog (S. cerevisiae) ENSG00000115561 NM_001005753.1 VPS24 Vacuolar protein sorting 24 NM_016079 homolog (S. cerevisiae) VPS37A Vacuolar protein sorting 37 homolog A (S. cerevisiae) ENSG00000073111 NM_004526 VPS72 Vacuolar protein sorting 72 ENSG00000163159 NM_005997 homolog (S. cerevisiae) ENSG00000100568 NM_006370 VTI1B Vesicle transport through interaction with t-SNAREs homolog 1B (yeast) ENSG00000167992 NM_152718 VWCE Von Willebrand factor C and EGF domains ENSG00000139668 NM_052950 WDFY2 WD repeat and FYVE domain containing 2 ENSG00000128815 WDFY4 WDFY family member 4 ENSG00000157796 NM_025132.3 WDR19 WD repeat domain 19 ENSG00000163811 WDR43 WD repeat domain 43 ENSG00000103091 NM_030581 WDR59 WD repeat domain 59 WDR85 WD repeat domain 85 ENSG00000166483 NM_003390 WEE1 WEE1 homolog (S. pombe) ENSG00000120662 NM_004294 WHSC2 Wolf-Hirschhorn syndrome ENSG00000185049 NM_005663 candidate 2 ENSG00000135925 NM_025216 WNT10A Wingless-type MMTV integration site family, member 10A ENSG00000169884 NM_003394 WNT10B Wingless-type MMTV integration site family, member 10B ENSG00000154767 NM_004628.3 XPC Xeroderma pigmentosum, complementation group C XR_016777.1 XR_019191.1 ENSG00000015532 NM_022167 XYLT2 Xylosyltransferase II YPEL3 Yippee-like 3 (Drosophila) ENSG00000182223 NM_175619 ZAR1 Zygote arrest 1 ENSG00000160062 NM_001040441 ZBTB8 Zinc finger and BTB domain ENSG00000215897 containing 8 ENSG00000100722 NM_024824 ZC3H14 Zinc finger CCCH-type NM_207660 containing 14 NM_207661 NM_207662 ENSG00000186908 NM_015336.2 ZDHHC17 Zinc finger, DHHC-type containing 17 ENSG00000180776 NM_153251.2 ZDHHC20 Zinc finger, DHHC-type containing 20 ZDHHC6 Zinc finger, DHHC-type containing 6 ENSG00000166140 NM_001077268.1 ZFYVE19 Zinc finger, FYVE domain containing 19 ENSG00000157077 NM_004799 ZFYVE9 Zinc finger, FYVE domain NM_007323 containing 9 NM_007324 ENSG00000156925 NM_003413 ZIC3 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila) ENSG00000186272 NM_006959.2 ZNF17 Zinc finger protein 17 ENSG00000105497 NM_007147 ZNF175 Zinc finger protein 175 ENSG00000188629 NM_003451 ZNF177 Zinc finger protein 177 ENSG00000178386 NM_013361 ZNF223 Zinc finger protein 223 ENSG00000171606 NM_016324.2 ZNF274 Zinc finger protein 274 NM_016325.2 NM_133502.1 ENSG00000181315 NM_024639 ZNF322A Zinc finger protein 322A ENSG00000188801 NM_199005 ZNF322B Zinc finger protein 322B ENSG00000175213 NM_024741 ZNF408 Zinc finger protein 408 ENSG00000112200 NM_001031623.2 ZNF451 Zinc finger protein 451 NM_015555 ZNF508 ENSG00000144331 NM_152520 ZNF533 Zinc finger protein 533 ENSG00000188171 NM_001076675.1 ZNF626 Zihc finger protein 626 NM_145297 ENSG00000198551 NM_145295.2 ZNF627 Zinc finger protein 627 ENSG00000175809 NM_152577 ZNF645 Zinc finger protein 645 ENSG00000161914 NM_138783 ZNF653 Zinc finger protein 653 ENSG00000156853 NM_138447 ZNF689 Zinc finger protein 689 ENSG00000167766 NM_018300 ZNF83 Zinc finger protein 83 ENSG00000106400 NM_006349 ZNHIT1 Zinc finger, HIT type 1

TABLE 7 miR-148b targets identified by miRanda and L2L Target Gene Accession No: Gene Name ARSE NM_000047.2 arylsulfatase E GI:157266308 (chondrodysplasia punctata 1) COL2A1 NM_001844.4 collagen, type II, alpha 1 (primary GI:111118975 osteoarthritis, spondyloepiphyseal dysplasia, congenital) COL2A1 NM_033150.2 collagen, type II, alpha 1 (primary GI:111118973 osteoarthritis, spondyloepiphyseal dysplasia, congenital) FBN1 NM_000138.3 fibrillin 1 GI:93589095 GHRHR NM_000823.2 growth hormone releasing GI:58530850 hormone receptor GHRHR NM_001009824.1 growth hormone releasing GI:58530852 hormone receptor HOXA2 NM_006735.3 homeobox A2 GI:37596298 HOXA5 NM_019102.2 homeobox A5 GI:24497516 LECT1 NM_007015.2 leukocyte cell derived chemotaxin 1 GI:59806341 LECT1 NM_001011705.1 leukocyte cell derived chemotaxin 1 GI:59806342 NOG NM_005450.2 Noggin GI:38788425 OSTF1 NM_012383.3 osteoclast stimulating factor 1 GI:38257156 PAPSS2 NM_001015880.1 3′-phosphoadenosine GI:62912491 5′-phosphosulfate synthase 2 PAPSS2 NM_004670.3 3′-phosphoadenosine GI:62912490 5′-phosphosulfate synthase 2 TFIP11 NM_012143.2 tuftelin interacting protein 11 GI:56788354 TFIP11 NM_001008697.1 tuftelin interacting protein 11 GI:56788355 TRPS1 NM_014112.2 trichorhinophalangeal syndrome I GI:90652850 

What is claimed is:
 1. A method of promoting mesenchymal stem cell (MSC) differentiation toward an osteogenic cell fate, the method comprising introducing into a MSC an effective amount of a composition comprising at least one differentiation promoting agent that is a mimic of miR-148b and an effective amount of an inhibitor of miR-489, wherein the inhibitor of miR-489 comprises a sequence that is the same as SEQ ID NO: 2, and the mimic of miR-148b comprises an antisense strand that comprises the sequence of SEQ ID NO:
 6. 